2-amino-quinoline derivatives

ABSTRACT

Described herein are 2-amino-quinoline derivatives that are agonists of toll-like receptors 7 and 8 (TLR7/8), pharmaceutical compositions, and methods of use of the compounds and compositions to treat various diseases, such as viral, cancer, and allergic diseases, in need thereof by administering a therapeutically effective amount of a 2-amino-quinoline derivative.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of, and priority to, Chinese PatentApplication Serial No. 201710287322.2, filed Apr. 27, 2017, the entiredisclosures of which are hereby incorporated by reference in theirentireties.

FIELD OF THE INVENTION

The present invention relates to 2-amino-quinoline derivatives, such asimidazoquinoline and pyrazoloquinoline analogs as agonists of toll-likereceptors 7 and 8 (TLR7 and TLR8), as well as pharmaceuticalcompositions comprising the same. The present invention also relates tothe use of the compounds, compositions, and the method of activatingTLR7 and TLR8 in treating various diseases.

BACKGROUND OF THE INVENTION

The TLR family plays a fundamental role in pathogen recognition andactivation of innate immunity. TLR7 and TLR8 are toll-like receptors 7and 8 respectively, and they lie in close proximity to each other on thehuman X chromosome. Both TLR7 and TLR8 recognize single-stranded RNA ofviruses such as HIV and HCV. TLR7 has been shown to play a significantrole in the pathogenesis of autoimmune disorders such as Systemic LupusErythematosus (SLE) as well as in the regulation of antiviral immunity.Genetic variants in TLR8 have recently been linked to susceptibility topulmonary tuberculosis. TLR7 is functional both in human and mouse,while TLR8 is only functional in human, but it seems to counteract TLR7activity. The major benefit of TLR7/8 agonists as immune responseenhancers is their simultaneous stimulation of several cell types. TLR7and TLR8 are expressed mostly on immune cells such as antigen presentingcells, including plasmacytoid dendritic cells (pDC) and myeloiddendritic cells (mDC), as well as natural killer cells, and macrophages.Activation of TLR7/8 on pDCs and mDCs results in the induction andrelease of type I interferons (IFN), tumor necrosis factor alpha (TNFα),and interleukin 12 (IL-12), which is an important step for theinitiation of innate and adaptive immunities to kill cancer cells. Forthese reasons, TLR7 and TLR8 have become interesting targets in bothantiviral and cancer therapy. There is also a growing interest in thetargeting of toll-like receptors, such as TLR7/8 for the treatment ofallergic diseases.

Small molecule agonists at TLR7 and TLR8 have increased interest in bothantiviral and cancer research own to their profound antiviral andantitumor activity. The lead compound of the imidazoquinoline family,imiquimod, is efficacious against many primary skin tumors and cutaneousmetastases and is marketed as a topical formulation. Resiquimod (R-848),from the same imidazoquinoline family, is a low molecular weightsynthetic molecule that activates immune cells via the TLR7/TLR8MyD88-dependent signaling pathway. It acts as an immune responsemodifier and has antiviral and antitumor activity. It has severalmechanisms of action, being both an agonist for toll-like receptors 7and 8, and an upregulator of the opioid growth factor receptor. R-848 isused as a topical gel in the treatment of skin lesions such as thosecaused by the herpes simplex virus and cutaneous T cell lymphoma, as anadjuvant to increase the effectiveness of vaccines, and as an adjuvantto immunotherapy in allergic rhinitis (AR) patient. Therefore, inaddition to their use as stand-alone immunotherapeutic agent, TLR7/8agonists hold promise as adjuvants in cancer vaccine or adoptive T celltransfer protocols. Extension of the families of the known syntheticTLR7/8 agonists, such as described above, pave the way to thedevelopment and identification of TLR7/8 agonists that are welltolerated, more selective with potent antitumor and antiviral activity,broadly applicable, and more effective as adjuvants.

SUMMARY OF THE INVENTION

Described herein are 2-amino-quinoline derivatives, pharmaceuticallyacceptable salts, solvates, prodrug and active metabolites, that areagonists of toll-like receptors 7 and 8 (TLR7/8). These compounds may beused to treat viral infection, such as HCV, cancer, and allergicdiseases in need thereof by administering a therapeutically effectiveamount of a 2-amino-quinoline derivative.

Some embodiments include a compound represented by Formula 1:

wherein a dashed line represents the presence or absence of a bond; A¹is CR¹, NR^(1A), or N; A² is CR², NR^(2A), O, or S; B¹ is CR⁵ or N; B²is CR⁶ or N; B³ is CR⁷ or N; R¹ and R² are independently F, Cl, Br, I,NO₂, CN, R^(a), —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a),—OCOR^(a), or —SO₂R^(a); X is a bond, O, NR^(a), —CO—, —SO—, or —SO₂—,—CONR^(a), hydrocarbyl , and R³ is H or C₁₋₃₀ organyl; or X—R³ is F orCl; R^(1A), R^(2A), R⁴, R^(a), and R^(b) are independently H or C₁₋₃₀organyl; R⁵, R⁶, and R⁷ are independently F, Cl, Br, I, NO₂, CN, R^(a),—OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a), —OCOR^(a), —SO₂R^(a),—SO₂NHR^(a), or —X¹—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)),—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein R⁵ and R⁶ or R⁶ and R⁷ canbe optionally linked to form a ring; wherein X¹ is a bond, O, NR^(a),—CO—, —SO—, or —SO₂—; Z is a bond, O, NHSO₂, or NHCO; m is 0, 1, 2, 3,4, 5, 6, 7, 8, 9, or 10; and n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.

Some embodiments include a pharmaceutical dosage form comprising asubject compound. A subject compound or a subject composition may beused for activating TLR7/8. In addition to its use as a stand-aloneimmunotherapeutic agent, such as an antiviral and anticancer agent, asubject compound or composition may be used as adjuvants in cancervaccine or adoptive T cell transfer protocols.

Some embodiments include a method of treating a disease or disorderassociated with a TLR7/8 agonist comprising administering an effectiveamount of a subject compound to a mammal in need thereof.

Some embodiments include use of a subject compound in the manufacture ofa medicament for the treatment of a disease or disorder associated witha TLR7/8 agonist.

DETAILED DESCRIPTION OF THE INVENTION

Unless otherwise indicated, when a compound or chemical structuralfeature, such as alkyl, alkenyl, alkynyl, aryl, heteroaryl, etc., isreferred to as being “optionally substituted,” it includes a featurethat has no substituents (i.e. unsubstituted), or a feature that is“substituted,” meaning that the feature has one or more substituents.The term “substituent” has the broadest meaning known to one of ordinaryskill in the art, and includes a moiety that occupies a positionnormally occupied by one or more hydrogen atoms attached to a parentcompound or structural feature. In some embodiments, a substituent maybe an ordinary organic moiety known in the art, which may have amolecular weight (e.g. the sum of the atomic masses of the atoms of thesubstituent) of 15-50 g/mol, 15-100 g/mol, 15-150 g/mol, 15-200 g/mol,15-300 g/mol, or 15-500 g/mol. In some embodiments, a substituentcomprises, or consists of: 0-30, 0-20, 0-10, or 0-5 carbon atoms; and0-30, 0-20, 0-10, or 0-5 heteroatoms, wherein each heteroatom mayindependently be: N, O, S, Si, F, Cl, Br, or I; provided that thesubstituent includes one C, N, O, S, Si, F, Cl, Br, or I atom. Examplesof substituents include, but are not limited to, alkyl, alkenyl,alkynyl, heteroalkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, acyl,acyloxy, alkylcarboxylate, thiol, alkylthio, cyano, halo, thiocarbonyl,O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido,N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato,isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl,haloalkoxyl, trihalomethanesulfonyl, trihalomethanesulfonamido, amino,etc.

For convenience, the term “molecular weight” is used with respect to amoiety or part of a molecule to indicate the sum of the atomic masses ofthe atoms in the moiety or part of a molecule, even though it may not bea complete molecule.

As used herein, the term “alkyl” has the broadest meaning generallyunderstood in the art and may include a moiety composed of carbon andhydrogen containing no double or triple bonds. Alkyl may be linearalkyl, branched alkyl, cycloalkyl, or a combination thereof and in someembodiments, may contain from one to thirty-five carbon atoms. In someembodiments, alkyl may include C₁₋₁₀ linear alkyl, such as methyl(—CH₃), methylene (—CH₂—), ethyl (—CH₂CH₃), ethylene (—C₂H₄—), propylene(—C₃CH₆—), n-butyl (—CH₂CH₂CH₂CH₃), n-pentyl (—CH₂CH₂CH₂CH₂CH₃), n-hexyl(—CH₂CH₂CH₂CH₂CH₂CH₃), etc.; C₃₋₁₀ branched alkyl, such as C₃H₇ (e.g.iso-propyl), C₄H₉ (e.g. branched butyl isomers), C₅H₁₁ (e.g. branchedpentyl isomers), C₆H₁₃ (e.g. branched hexyl isomers), C₇H₁₅ (e.g. heptylisomers), etc.; C₃₋₁₀ cycloalkyl, such as C₃H₅ (e.g. cyclopropyl), C₄H₇(e.g. cyclobutyl isomers such as cyclobutyl, methylcyclopropyl, etc.),C₅H₉ (e.g. cyclopentyl isomers such as cyclopentyl, methylcyclobutyl,dimethylcyclopropyl, etc.) C₆H₁₁ (e.g. cyclohexyl isomers), C₇H₁₃ (e.g.cycloheptyl isomers), etc.; and the like.

As used herein the term “aryl” includes a group that can be derived froma monocyclic and polycyclic aromatic hydrocarbon by removal of ahydrogen atom from a ring carbon atom. The “aryl” may include anaromatic ring or aromatic ring system such as phenyl, naphthyl, etc.

The term “heteroaryl” has the broadest meaning understood by a person ofordinary skill in the art and includes an “aryl” which has one or moreheteroatoms in the ring or ring system, such as pyridinyl, furyl,thienyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, oxadiazolyl,isoxazolyl, indolyl, quinolinyl, benzofuranyl, benzothienyl,benzooxazolyl, benzothiazolyl, benzoimidazolyl, etc.

Unless otherwise indicated, any reference to a compound herein bystructure, name, or any other means includes pharmaceutically acceptablesalts, such as HCl, HBr, HI, H₂SO₄, acetate, citrate, phosphate, sodium,potassium, and ammonium salts; prodrugs, such as ester prodrugs;alternate solid forms, such as polymorphs, solvates, hydrates, etc.;tautomers; or any other chemical species that may rapidly convert to acompound described herein under conditions in which the compounds areused as described.

If stereochemistry is not indicated, a name or structural representationincludes any stereoisomer or any mixture of stereoisomers.

For the purposes of this disclosure, “treat,” “treating,” or “treatment”includes use of a compound, composition, therapeutically active agent,or drug in the diagnosis, cure, mitigation, treatment, or prevention ofdisease or other undesirable condition.

With respect to any relevant structural representation, such as Formula1, a dashed line represents the presence or absence of a bond. Forexample, compounds represented by Formulas 1A and 1B are included.

With respect to any relevant structural representation, such as Formula1, 1A, or 1B, A¹ is CR¹, NR^(1A), or N. In some embodiments, A¹ is CR¹.In some embodiments, A¹ is NR^(1A). In some embodiment, A¹ is N.

With respect to any relevant structural representation, such as Formula1, 1A, or 1B A² is CR², NR^(2A), O, or S. In some embodiments, A² isCR². In some embodiments, A² is NR^(2A). In some embodiments, A² is O.In some embodiments, A² is S.

With respect to any relevant structural representation, such as Formula1, 1A, or 1B, X is a bond, O, NR^(a), —C(═O)—, —S(═O)—, —S(═O)₂—,—CONR^(a), hydrocarbyl, and R³ is H or C₁₋₃₀ organyl; or X—R³ is F orCl. In some embodiments, X is a bond. In some embodiments, X is O. Insome embodiments, X is NR^(a). In some embodiments, X is —C(═O)—. Insome embodiments, X is —S(═O)—. In some embodiments, X is —S(═O)₂—. Insome embodiments, X—R³ is F. In some embodiment, X—R³ is Cl.

With respect to any relevant structural representation, such as R^(a),NR^(a), —OR^(a), —OCOR^(a), or —SO₂R^(a), —NR^(a)R^(b), in such asFormula 1, 1A or 1B, R^(a) or R^(b) is independently H or organyl, suchas C₁₋₃₀ organyl, including any organic substituent group, regardless offunctional type, having a free valence at a carbon, such as optionallysubstituted alkyl, e.g. optionally substituted C₁₋₃₀, C₁₋₁₂, C₁₋₆, orC₁₋₃ alkyl, including methyl, ethyl, C₃ alkyl, C₄ alkyl, C₅ alkyl, C₆alkyl, C₇ alkyl, C₈ alkyl, C₉ alkyl, C₁₀ alkyl, C₁₁ alkyl, C₁₂ alkyl,C₁₃ alkyl, C₁₄ alkyl, C₁₅ alkyl, C₁₆ alkyl, C₁₇ alkyl, C₁₈ alkyl, C₁₉alkyl, C₂₀ alkyl, C₂₁ alkyl, C₂₂ alkyl, C₂₃ alkyl, C₂₄ alkyl, C₂₅ alkyl,C₂₆ alkyl, C₂₇ alkyl, C₂₈ alkyl, C₂₉ alkyl, C₃₀ alkyl, C₃ cycloalkyl, C₄cycloalkyl, C₅ cycloalkyl, C₆ cycloalkyl, C₇ cycloalkyl, C₈ cycloalkyl,C₉ cycloalkyl, C₁₀ cycloalkyl, C₁₁ cycloalkyl, C₁₂ cycloalkyl, etc.;optionally substituted alkenyl, e.g. optionally substituted C₂₋₁₂ orC₂₋₆, alkenyl, including ethenyl, C₃ alkenyl, C₄ alkenyl, C₅ alkenyl, C₆alkenyl, C₇ alkenyl, C₈ alkenyl, C₉ alkenyl, C₁₀ alkenyl, C₁₁ alkenyl,C₁₂ alkenyl, C₄ cycloalkenyl, C₅ cycloalkenyl, C₆ cycloalkenyl, C₇cycloalkenyl, C₈ cycloalkenyl, C₉ cycloalkenyl, C₁₀ cycloalkenyl, C₁₁cycloalkenyl, C₁₂ cycloalkenyl, etc.; optionally substituted alkynyl,e.g. optionally substituted C₂₋₁₂ or C₂₋₆ alkynyl, including ethynyl, C₃alkynyl, C₄ alkynyl, C₅ alkynyl, C₆ alkynyl, C₇ alkynyl, C₈ alkynyl, C₉alkynyl, C₁₀ alkynyl, C₁₁ alkynyl, C₁₂ alkynyl, C₅ cycloalkynyl, C₆cycloalkynyl, C₇ cycloalkynyl, C₈ cycloalkynyl, C₉ cycloalkynyl, C₁₀cycloalkynyl, C₁₁ cycloalkynyl, C₁₂ cycloalkynyl, etc.; optionallysubstituted aryl, such as optionally substituted phenyl, optionallysubstituted naphthyl, etc.; optionally substituted heterocyclyl,optionally substituted heteroaryl, etc.; organyl also includes CN,—C(O)R^(a), —C(O)OR^(a), —C(O)NHR^(a), —C(O)NR^(a)R^(b),—C(O)—Z-organyl, wherein Z is a bond, O, S, or NR^(a)R^(b),—C(R^(a)R^(b))—OR^(a), —C(R^(a)R^(b))—NR^(a)R^(b). In some embodiments,R^(a) or R^(b) is independently H or C₁₋₃₀ hydrocarbyl, such as alkyl,alkenyl, alkynyl, or phenyl. In some embodiments, C₁₋₃₀ organyl can besubstituted by halogen, hydroxyl, amines, alkoxyl, aryl, heteroaryl,sulfone, sulfonamide, carboxylic acid, amide, reversed amide, ester,cycloalkyl, heterocycloalkyl, carbonyl, alkyl, alkenyl, alkynyl,phosphonamidic acid, phosphinic amide, or phosphine oxide.

Some embodiments include a compound of Formula 2 or Formula 2A.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, or 2A, B¹ is CR⁵ or N. In some embodiments, B¹ is CR⁵. Insome embodiments, B¹ is N.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, or 2A, B² is CR⁶ or N. In some embodiments, B² is CR⁶. Insome embodiments, B² is N.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, or 2A, B³ is CR⁷ or N. In some embodiments, B³ is CR⁷. Insome embodiments, B³ is N.

Some embodiments include a compound of Formula 3A, 3B, 3C, 3D, 3E, 4, 5,6, 7, 8, 9, 10, 11, 12, or 13.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 3E, 4, 5, 6, 7, 8, 9, 10, 11, 12, or13, R¹ or R^(1A) is independently H or any substituent, such as F, Cl,Br, I, NO₂, CN, R^(a), —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a),—OCOR^(a), or —SO₂R^(a). In some embodiments, R¹ or R^(1A) isC_(r)H_(2r+1)O, wherein r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, includingC₂H₅O, such as —(CH₂)₂OH; C₃H₇O, such as —CH₂OCH₂CH₃, —(CH₂)₂OCH₃, etc.;C₁₋₁₂ alkyl, such as —(CH₂)₃CH₃, —CH₂CH₂CH(CH₃)₂.

In some embodiments, R¹ or R^(1A) is —(CH₂)₂OH. In some embodiments, R¹or R^(1A) is —CH₂OCH₂CH₃. In some embodiments, R¹ or R^(1A) is—(CH₂)₂OCH₃. In some embodiments, R¹ or R^(1A) is —(CH₂)₃CH₃. In someembodiments, R¹ or R^(1A) is —CH₂CH₂CH(CH₃)₂.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 4, 5, 6, 7, 8, 9, or 10, R² or R^(2A) isindependently H or any substituent, such as —CH₃, —CH₂CH(CH₃)₂,—CH₂C(CH₃)₂R⁸, —CH₂CH₂C(CH₃)₂R⁸, —C₄H₉O, —CH₂CH₂OCH(CH₃)₂.

In some embodiments, R² or R^(2A) is H. In some embodiments, R² orR^(2A) is CH₃. In some embodiments, R² or R^(2A) is —CH₂CH(CH₃)₂. Insome embodiments, R² or R^(2A) is —CH₂C(CH₃)2R⁸. In some embodiments, R²or R^(2A) is —CH₂C(CH₃)₂OH. In some embodiments, R² or R^(2A) is—CH₂CH₂C(CH₃)₂OH. In some embodiments, R² or R^(2A) is —CH₂CH₂OCH(CH₃)₂.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 4, 5, 6, 7, 8, 9, or 10, R³ is anysubstituent, such as CH₁₋₃₀ optionally substituted alkyl,—C_(w)H_(2w+1)O or an ester thereof, wherein w is 0, 1, 2, 3, 4, 5, 6,7, 8, 9, or 10; —(C_(u)H_(2u)O₀₋₁)—Z—(C_(v)H_(2v+1)), wherein Z is abond, O, NHSO₂, or NHCO, u is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and vis 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, or 24; or —(C_(t)H_(2t)O₀₋₁)-Ht, wherein t is 0, 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, andHt is optionally substituted C₃₋₁₀ heterocyclyl.

In some embodiments, R³ is H. In some embodiment, R³ is CH₃. In someembodiments, R³ is —CH₂CH(CH₃)₂ In some embodiments, R³ is—(CH₂)₂CH(CH₃)₂. In some embodiments, R³ is —CH₂CH(OH)CH₃. In someembodiments, R³ is —(CH₂)₂CH(OH)CH_(3.) In some embodiments, R³ is—(CH₂)₂C(CH₃)₂OH. In some embodiments, R³ is (CH₂)₂OCH(CH₃)₂,—(CH₂)₃NHSO₂CH₃, —(CH₂)₄NHSO₂CH₃, —(CH₂)₂O (CH₂)₂NHSO₂CH₃,—(CH₂)₃NHCOCH₁₇H₃₅, —(CH₂)₃NHCOCH₃, —(CH₂)₄NHCOCH₃, —(CH₂)₄NHCOC₁₇H₃₅,—(CH₂)₃NH₂,

With respect to any relevant structural representation, such as Formula3E, R³ is C₁₋₃ alkyl optionally substituted with 1 to 6 of R^(8A), sameor different, wherein R^(8A) is OH, oxide, C₁₋₆ organyl, or —O—(C₁₋₆organyl).

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 3E, 4, 5, 6, 7, 8, 9, 10, 11, 12, or13, R⁴ is H or any substituent, such as hydrocarbyl.

In some embodiments, R⁴ is H.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 3E, 4, 5, 6, 7, 8, 9, 10, 11, 12, or13, R⁵ is H or any substituent, such as F, Cl, R^(a), —CO₂R^(a),—CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a),—OCOR^(a), or —SO₂R^(a), wherein R^(a) and R^(b) are independently H orC₁₋₃₀ organyl. In some embodiments, R⁵ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, —NHSO₂, or—NHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6. 7. 8. 9. 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or24. In some embodiments, R⁵ is H.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 3E, 4, 5, 6, 7, 8, 9, 10, 11, 12, or13, R⁶is H or any substituent, such as F, Cl, R^(a), —CO₂R^(a),—CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a),—OCOR^(a), or —SO₂R^(a), wherein R^(a) and R^(b) are independently H orC₁₋₃₀ organyl. In some embodiment, R⁶ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, —NHSO₂, or—NHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or24. In some embodiments, R⁶ is H.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 3E, 4, 5, 6, 7, 8, 9, 10, 11, 12, or13, R⁷ is H or any substituent, such as F, Cl, R^(a), —CO₂R^(a),—CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a),—OCOR^(a), or —SO₂R^(a), wherein R^(a) and R^(b) are independently H orC₁₋₃₀ organyl. In some embodiment, R⁷ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, —NHSO₂, or—NHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or24. In some embodiments, R⁷ is H.

With respect to any relevant structural representation, such as Formula4, 5, 6, 7, 8, 9, or 10, R⁸ is H, OH or C₁₋₆ alkyl. In some embodiments,R⁸ is H. In some embodiments, R⁸ is OH. In some embodiment, R⁸ is CH₃.

With respect to any relevant structural representation, such as Formula3E, R^(8A) is OH, oxide, C₁₋₆ organyl, or —O—(C₁₋₆ organyl). 1 to 6,same or different R^(8A) can be attached at any ring C-atom. In someembodiments, R^(8A) is OH. In some embodiments, R^(8A) is CH₃. In someembodiments, two different R^(8A), such as CH₃ and OH, are attached to asame ring C-atom. In some embodiments, R^(8A) is —C(CH₃)₂OH.

With respect to any relevant structural representation, such as Formula1, 1A, 1B, 2, 2A, 3A, 3B, 3C, 3D, 4, 5, 6, 7, 8, 9, or 10, in someembodiment, R³ and R⁴ are independently H or C₁₋₁₂ organyl; R¹, R², R⁵,R⁶, and R⁷ are independently F, Cl, Br, I, NO₂, CN, —OR^(a),—NR^(a)R^(b), —OCOR^(a), or —SO₂R^(a); R^(1A) and R^(2A) are R^(a);R^(a) and R^(b) are independently H or C₁₋₁₂ organyl; and R⁸ is H or OH.In some embodiment, R⁵ and R⁶ or R⁶ and R⁷ can be optionally linked toform a saturated or an unsaturated ring.

Some embodiments include optionally substituted9-methoxy-1H-imidazo[4,5-c]quinolin-4-amine or a salt thereof.

Some embodiments include optionally substituted1-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-isobutyl-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-(4-amino-9-methoxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol or a salt thereof;optionally substituted1-(4-amino-2-(2-hydroxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1H-imidazo[4,5-c]quinolin-4-amine or asalt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butan-2-olor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; or optionally substituted4-((4-amino-2-(ethoxymethyl)-1-isobutyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-(2-isopropoxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted4-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1H-imidazo[4,5-c]quinolin-4-amine or a saltthereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)methanesulfonamideor a salt thereof; optionally substitutedN-(2-(2-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)ethoxy)ethyl)-methanesulfonamideor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)acetamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)methanesulfonamideor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)stearamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)acetamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)-stearamideor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(2-morpholinoethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-((tetrahydrofuran-3-yl)oxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(pyrrolidin-3-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(piperidin-4-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)palmitamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)palmitamideor a salt thereof; optionally substituted9-(3-aminopropoxy)-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isopropoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylpropan-2-ol or a salt thereof; optionallysubstituted2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-10-amineor a salt thereof; optionally substituted(R)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino-[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted2-amino-12-(ethoxymethyl)-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6(7H)-oneor a salt thereof; or optionally substituted tert-butyl4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)piperidine-1-carboxylateor a salt thereof.

TABLE 3 Compound Name Structure9-methoxy-1H-imidazo[4,5-c]quinolin-4-amine

1-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

2-(ethoxymethyl)-1-isobutyl-9-methoxy-1H- imidazo[4,5-c]quinolin-4-amine

1-(4-amino-9-methoxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

1-(4-amino-2-(2-hydroxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-ol

2-(ethoxymethyl)-9-(isopentyloxy)-1H- imidazo[4,5-c]quinolin-4-amine

4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butan-2-ol

1-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propan-2-ol

4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-ol

4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan- 2-ol

2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1H-imidazo[4,5-c]quinolin-4-amine

4-((4-amino-2-(ethoxymethyl)-1-isobutyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan- 2-ol

2-(ethoxymethyl)-1-(2-isopropoxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amine

4-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylbutan-2-ol

2-(ethoxymethyl)-9-isobutoxy-1H-imidazo[4,5- c]quinolin-4-amine

2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amine

2-(ethoxymethyl)-9-isobutoxy-1-methyl-1H- imidazo[4,5-c]quinolin-4-amine

2-(ethoxymethyl)-9-isobutoxy-1-methyl-1H- imidazo[4,5-c]quinolin-4-amine

N-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)propyl)methanesulfonamide

N-(2-(2-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9- yl)oxy)ethoxy)ethyl)methanesulfonamide

N-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)propyl)acetamide

N-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)butyl)methanesulfonamide

N-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)propyl)stearamide

N-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)acetamide

N-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)stearamide

2-(ethoxymethyl)-1-methyl-9-(2-morpholinoethoxy)-1H-imidazo[4,5-c]quinolin-4- amine

2-(ethoxymethyl)-1-methyl-9-((tetrahydrofuran-3-yl)oxy)-1H-imidazo[4,5-c]quinolin-4-amine

2-(ethoxymethyl)-1-methyl-9-(pyrrolidin-3-yloxy)-1H-imidazo[4,5-c]quinolin-4-amine

2-(ethoxymethyl)-1-methyl-9-(piperidin-4-yloxy)-1H-imidazo[4,5-c]quinolin-4-amine

N-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)propyl)palmitamide

N-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H- imidazo[4,5-c]quinolin-9-yl)oxy)butyl)palmitamide

9-(3-aminopropoxy)-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amine

2-(ethoxymethyl)-9-isopropoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amine

1-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2- methylpropan-2-ol

2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-10-amine

(R)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3- yl)propan-2-ol

(S)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3- yl)propan-2-ol

(S)-2-amino-12-(ethoxymethyl)-6-methyl-6,7- dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin- 6-ol

(R)-2-amino-12-(ethoxymethyl)-6-methyl-6,7- dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin- 6-ol

(R)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2- de]quinolin-6-ol

(S)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2- de]quinolin-6-ol

2-amino-12-(ethoxymethyl)-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin- 6(7H)-one

tert-butyl 4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9- yl)oxy)piperidine-1-carboxylate

Some embodiments include optionally substituted4-amino-2H-pyrazolo[3,4-c]quinolin-9-ol or a salt thereof; or optionallysubstituted 4-amino-2-isopentyl-2H-pyrazolo[3,4-c]quinolin-9-ol or asalt thereof; optionally substituted2-isopentyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or asalt thereof; or optionally substituted2-butyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or a saltthereof.

TABLE 4 Compound Name Structure 4-amino-2H-pyrazolo[3,4-c]quinolin-9-ol

4-amino-2-isopentyl-2H-pyrazolo[3,4-c]quinolin- 9-ol

2-isopentyl-9-(isopentyloxy)-2H-pyrazolo[3,4- c]quinolin-4-amine

2-butyl-9-(isopentyloxy)-2H-pyrazolo[3,4- c]quinolin-4-amine

The following embodiments are specifically contemplated herein.

Embodiment 1

A compound represented by a formula:

or a salt thereof;

wherein a dashed line represents the presence or absence of a bond;

A¹ is CR¹, NR^(1A), or N;

A² is CR², NR^(2A), O, or S;

B¹ is CR⁵ or N;

B² is CR⁶ or N;

B³ is CR⁷ or N;

R³ and R² are independently F, Cl, Br, I, NO₂, CN, R^(a), —OR^(a),—NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a), —OCOR^(a), or —SO₂R^(a);

X is a bond, O, NR^(a), —CO—, —SO—, or —SO₂—, —CONR^(a), hydrocarbyl,and R³ is H or C₁₋₃₀ organyl; or X—R³ is F or Cl;

R^(1A), R^(2A), R⁴, R^(a), and R^(b) are independently H or C₁₋₃₀organyl;

R⁵, R⁶, and R⁷ are independently F, Cl, Br, I, NO₂, CN, R^(a), —OR^(a),—NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a), —OCOR^(a), —SO₂R^(a), or—X¹—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)),—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein R⁵ and R⁶ or R⁶ and R⁷ canbe optionally linked to form a ring;

wherein X¹ is a bond, O, NR^(a), —CO—, —SO—, or —SO₂—;

Z is a bond, O, NHSO₂, or NHCO;

m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, or 23.

Embodiment 2

The compound of embodiment 1, further represented by a formula:

or a salt thereof, wherein R³ is C₁₋₃₀ organyl. In some embodiments, R³is C₁₋₃ alkyl optionally substituted with 1 to 6 R^(8A) groups, whereineach R^(8A) group is independently OH, oxide, C₁₋₆ organyl, or —O—(C₁₋₆organyl).

Embodiment 3

The compound of embodiment 1, further represented by a formula:

or a salt thereof;wherein R⁴ is H, C₁₋₃₀ non-aromatic organyl, or C₁₋₃₀ aromatic organylcontaining an aromatic group that is not directly attached to the Natom.

Embodiment 4

The compound of embodiment 1, 2 or 3, wherein R¹ or R^(1A) is C₁₋₁₂optionally substituted alkyl.

Embodiment 5

The compound of embodiment 4, wherein R¹ or R^(1A) is —C_(r)H_(2r+1)O,or an ester thereof, wherein r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

Embodiment 6

The compound of embodiment 5, wherein R¹ or R^(1A) is —C₃H₇O.

Embodiment 7

The compound of embodiment 6, wherein R¹ or R^(1A) is —CH₂OCH₂CH₃.

Embodiment 8

The compound of embodiment 1, 2, 3, 4, 5, 6, or 7, wherein R² or R^(2A)is H or C₁₋₁₂ optionally substituted alkyl.

Embodiment 9

The compound of embodiment 8, wherein R² or R^(2A) is C₁₋₆ alkyl, or—C_(y)H_(2y+1)O or an ester thereof, wherein y is 1, 2, 3, 4, 5, 6, 7,8, 9, or 10.

Embodiment 10

The compound of embodiment 9, wherein R² or R^(2A) is —C₄H₉O.

Embodiment 11

The compound of embodiment 10, wherein R² or R^(2A) is —CH₂—CH(CH₃)₂—OH.

Embodiment 12

The compound of embodiment 8, wherein R² or R^(2A) is H.

Embodiment 13

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12,wherein R³ is C₁₋₃₀ optionally substituted alkyl.

Embodiment 14

The compound of embodiment 13, wherein R³ is C₁₋₁₀ alkyl, or—C_(w)H_(2w+1)O or an ester thereof, wherein w is 1, 2, 3, 4, 5, 6, 7,8, 9, or 10.

Embodiment 15

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13,wherein R³ is —(C_(t)H_(2t)O₀₋₁)-Ht, wherein t is 0, 1, 2, 3, 4, 5, 6,7, 8, 9, or 10, and Ht is optionally substituted C₃₋₆ heterocyclyl.

Embodiment 16

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13,wherein R³ is —(C_(u)H_(2u)O₀₋₁)—Z—(C_(v)H_(2v+1)), wherein Z is a bond,O, NHSO₂, or NHCO, u is 0, 1, 2, 3, 4, 5, or 6, and v is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.

Embodiment 17

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13,wherein R³ is —(C_(u)H_(2u)O₀₋₁)—NR^(a)R^(b), and u is 1, 2, 3, 4, 5, or6, wherein R^(a) and R^(b) are independently H or C₁₋₆ alkyl.

Embodiment 18

The compound of embodiment 14, wherein R³ is C₅H₁₁O.

Embodiment 19

The compound of embodiment 18, wherein R³ is —CH₂—CH₂—CH(CH₃)₂OH.

Embodiment 20

The compound of embodiment 17, wherein R³ is —CH₂—CH₂—CH₂—NH₂.

Embodiment 21

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, or 20, wherein R⁴ is H or C₁₋₆ alkyl.

Embodiment 22

The compound of embodiment 21, wherein R⁴ is H.

Embodiment 23

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, or 22, wherein R⁵ is R^(a), F, Cl,—CO₂R^(a), —CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —OCOR^(a), or—SO₂R^(a), wherein R^(a) and R^(b) are independently H or C₁₋₆ alkyl.

Embodiment 24

The compound of embodiment 23, wherein R⁵ is H.

Embodiment 25

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, or 22, wherein R⁵ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, NHSO₂, orNHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24or 25.

Embodiment 26

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25, wherein R⁶ is R^(a),F, Cl, —CO₂R^(a), —CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —OCOR^(a),or —SO₂R^(a), wherein R^(a) and R^(b) are independently H or C₁₋₆ alkyl.

Embodiment 27

The compound of embodiment 26, wherein R⁶ is H.

Embodiment 28

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25, wherein R⁶ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, NHSO₂, orNHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.

Embodiment 29

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28, wherein R⁷is R^(a), F, Cl, —CO₂R^(a), —CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b),—OCOR^(a), or —SO₂R^(a), R^(a) and R^(b) are independently H or C₁₋₆alkyl.

Embodiment 30

The compound of embodiment 29, wherein R⁷ is H.

Embodiment 31

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28, whereinR⁷ is —(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O,NHSO₂, or NHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,or 23.

Embodiment 32

The compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or31, R⁸ is H, OH, or CH₃.

Embodiment 33

The compound of embodiment 32, wherein R⁸ is OH.

Embodiment 34

The compound of embodiment 32, wherein R⁸ is H.

Embodiment 35

A compound, which is:

a salt of any of these compounds, or an ester of any of these compoundshaving an —OH group.

Embodiment 36

A compound which is optionally substituted9-methoxy-1H-imidazo[4,5-c]quinolin-4-amine.

Embodiment 37

A compound which is optionally substituted9-methoxy-2H-pyrazolo[3,4-c]quinolin-4-amine.

Embodiment 38

The compound of embodiment 36, which is optionally substituted1-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-isobutyl-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-(4-amino-9-methoxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted1-(4-amino-2-(2-hydroxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1H-imidazo[4,5-c]quinolin-4-amine or asalt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butan-2-olor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1-isobutyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-(2-isopropoxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted4-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1H-imidazo[4,5-c]quinolin-4-amine or a saltthereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)methanesulfonamideor a salt thereof; optionally substitutedN-(2-(2-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)ethoxy)ethyl)-methanesulfonamide or a salt thereof;optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)acetamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)methane-sulfonamideor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)stearamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)acetamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)-stearamide or a salt thereof; optionallysubstituted2-(ethoxymethyl)-1-methyl-9-(2-morpholinoethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-((tetrahydrofuran-3-yl)oxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(pyrrolidin-3-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(piperidin-4-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)palmitamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)palmitamide or a salt thereof; optionallysubstituted9-(3-aminopropoxy)-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isopropoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylpropan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-10-amineor a salt thereof; optionally substituted(R)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino-[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted2-amino-12-(ethoxymethyl)-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6(7H)-oneor a salt thereof; or optionally substituted tert-butyl4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)piperidine-1-carboxylateor a salt thereof.

Embodiment 39

The compound of embodiment 37 which is optionally substituted4-amino-2H-pyrazolo[3,4-c]quinolin-9-ol or a salt thereof; optionallysubstituted 4-amino-2-isopentyl-2H-pyrazolo[3,4-c]quinolin-9-ol or asalt thereof; optionally substituted2-isopentyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or asalt thereof; or optionally substituted2-butyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or a saltthereof.

Embodiment 40

A method of treating viral infection, cancer, or an allergic disease,comprising administering a compound according to embodiment 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36 37, 38, or 39, to amammal in need thereof.

Embodiment 41

Use of a compound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, or 39, in the manufacture of amedicament for the treatment of viral infection, cancer, or an allergicdisease.

Embodiment 42

The method of embodiment 40 or use of embodiment 41, wherein the viralinfection comprises HCV infection.

Embodiment 43

A dosage form suitable for administration to a mammal, comprising acompound of embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, or 39.

EXAMPLES

In the synthetic schemes described below, unless otherwise indicated alltemperatures are set forth in degrees Celsius and all parts andpercentages are by weight. Reagents and solvents were purchased fromcommercial suppliers such as Aldrich Chemical Company and were usedwithout further purification unless otherwise indicated. Tetrahydrofuran(THF) and N,N-dimethylforamide (DMF) were purchased from commercialsources in Sure Seal bottles and used as received.

The reactions set forth below were done generally under a positivepressure of argon or nitrogen at an ambient temperature (unlessotherwise stated) in anhydrous solvents. Glassware was oven dried and/orheat dried. The reactions were assayed by TLC and/or analyzed by LC-MSand terminated as judged by the consumption of starting material.Analytical thin layer chromatography (TLC) was performed on glass platespre-coated with silica gel 60 F254 0.25 mm plates (EM Science), andvisualized with UV light (254 nm) and/ or heating with commercialethanolic phosphomolybdic acid. Preparative thin layer chromatography(TLC) was performed on glass-plates pre-coated with silica gel 60 F2540.5 mm plates (20×20 cm, from commercial sources) and visualized with UVlight (254 nm).

Work-ups were typically done by doubling the reaction volume with thereaction solvent or extraction solvent and then washing with theindicated aqueous solutions using 25% by volume of the extraction volumeunless otherwise indicated. Product solutions were dried over anhydrousNa₂SO₄ and/or Mg₂SO₄ prior to filtration and evaporation of the solventsunder reduced pressure on a rotary evaporator and noted as solventsremoved in vacuo. Column chromatography was completed under positivepressure using 230-400 mesh silica gel.

¹H-NMR spectra and ¹³C-NMR were recorded on a Varian Mercury-VX400instrument operating at 400 MHZ. NMR spectra were obtained as CDCl₃solutions (reported in ppm), using chloroform as the reference standard(7.27 ppm for the proton and 77.00 ppm for carbon), CD₃OD (3.4 and 4.8ppm for the protons and 49.3 ppm for carbon), DMSO-d₆ (2.49 ppm forproton), or internally tetramethylsilane (0.00 ppm) when appropriate.Other NMR solvents were used as needed.

Example 1 Synthesis of1-[4-Amino-2-(ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol

Step 1: Synthesis of1-[(5-Methoxy-3-nitro-4-quinolyl)amino]-2-methyl-propan-2-ol

To a solution of 1-amino-2-methyl-propan-2-ol (747.10 mg, 8.38 mmol, 2.0eq.) and Et₃N (2.12 g, 20.95 mmol, 2.90 mL, 5.0 eq.) in DCM (50.00 mL)was added 4-chloro-5-methoxy-3-nitro-quinoline (1.00 g, 4.19 mmol, 1.0eq.). The resulting mixture was stirred at 25° C. for 0.5 h. Thereaction mixture was washed with water (30 mL) and brine (30 mL) viaextraction. The organic phase was dried over anhydrous Na₂SO₄, filtered,and concentrated in vacuo. The residue was purified with columnchromatography (DCM to DCM/MeOH=20/1). The desired product of1-[(5-methoxy-3-nitro-4-quinolyl)amino]-2-methyl-propan-2-ol (1.00 g,3.43 mmol, 81.86% yield) was obtained as a yellow solid. ¹H NMR (400MHz, CDCl₃) δ ppm: 9.51 (s, 1H), 9.03 (s, 1H), 7.63 (t, J=8.0 Hz, 1H),7.58 (d, J=8.4 Hz, 1H), 6.94 (d, J=7.2 Hz, 1H), 4.10 (s, 3H), 2.95 (d,J=4.8 Hz, 2H), 1.29 (s, 6H); ES-LCMS m/z 292.3 [M+H]⁺.

Step 2: Synthesis of1-[(3-Amino-5-methoxy-4-quinolyl)amino]-2-methyl-propan-2-ol

To a solution of1-[(5-methoxy-3-nitro-4-quinolyl)amino]-2-methyl-propan-2-ol (1.00 g,3.43 mmol, 1.0 eq.) in MeOH (100.00 mL) was added Raney-Ni (626.42 mg,7.31 mmol, 2.1 eq.) under N₂. The suspension was degassed under vacuumand purged with H₂ several times. The resulting mixture was stirredunder H₂ (15 psi) at 25° C. for 3 h. The reaction mixture was filtered.The filtrate was concentrated in vacuo. The desired product of1-[(3-amino-5-methoxy-4-quinolyl)amino]-2-methyl-propan-2-ol (870.00 mg,3.33 mmol, 97.08% yield) was obtained as a yellow solid. ¹H NMR (400MHz, CD₃OD) δ ppm: 8.26 (s, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.31 (t, J=8.0Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 4.02 (s, 3H), 3.22 (s, 2H), 1.29 (s,6H); ES-LCMS m/z 262.3 [M+H]⁺.

Step 3: Synthesis of1-[2-(Ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol

A solution of1-[(3-amino-5-methoxy-4-quinolyl)amino]-2-methyl-propan-2-ol (400.00 mg,1.53 mmol, 1.0 eq.) and 4 Å MS (200 mg) in 2-ethoxyacetic acid (3.30 g,31.7 mmol, 3 mL, 20.7 eq.) was stirred at 120° C. for 4 h undermicrowave. The reaction mixture was then filtered. The filtrate wasdissolved in DCM (80 mL) and adjusted to pH=8 with 2 M NaOH. The organiclayer was separated and dried over anhydrous Na₂SO₄, filtered andconcentrated in vacuo. The mixture was purified with columnchromatography (DCM to DCM/MeOH=10/1). The desired product of1-[2-(ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol(230.00 mg, 698.26 μmol, 45.62% yield) was obtained as a yellow solid.¹H NMR (400 MHz, CD₃OD) δ ppm: 9.09 (s, 1H), 7.79 (d, J=8.0 Hz, 1H),7.67 (t, J=8.2 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 5.68 (s, 1H), 5.39 (s,1H), 4.63 (m, 2H), 4.14 (s, 3H), 3.62 (m, 2H), 1.32-1.26 (m, 3H),1.25-1.23 (m, 3H), 0.76 (m, 3H); ES-LCMS m/z: 330.3 [M+H]⁺.

Step 4: Synthesis of1-[2-(Ethoxymethyl)-9-methoxy-5-oxido-imidazo[4,5-c]quinolin-5-ium-1-yl]-2-methyl-propan-2-ol

To a solution of1-[2-(ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol(230.00 mg, 698.26 μmol, 1.0 eq.) in DCM (30.00 mL) was added m-CPBA(212.64 mg, 1.05 mmol, 85% purity, 1.5 eq.). The resulting mixture wasstirred at 25° C. for 1 h. The reaction mixture was then adjusted topH=8 with aqueous K₂CO₃ and partitioned between DCM (50 mL) and water(20 mL). The organic layer was separated, washed with brine (20 mL),dried over Na₂SO₄, and filtered. After filtration, the filtrate wasconcentrated in vacuo. The residue was purified with prep-TLC(DCM/MeOH=8/1, R_(f)=0.3). The desired product of1-[2-(ethoxymethyl)-9-methoxy-5-oxido-imidazo[4,5-c]quinolin-5-ium-1-yl]-2-methyl-propan-2-ol(150.00 mg, 434.29 μmol, 62.20% yield) was obtained as a yellow solid.¹H NMR (400 MHz, CD₃OD) δ ppm: 9.10 (s, 1H), 8.52 (d, J=8.8 Hz, 1H),7.85 (t, J=8.6 Hz, 1H), 7.45 (d, J=7.6 Hz, 1H), 5.54 (s, 1H), 5.31 (s,1H), 4.58 (s, 2H), 4.19 (s, 3H), 3.62 (m, 2H), 1.28-1.23 (m, 6H), 0.84(m, 3H); ES-LCMS m/z: 346.3 [M+H]⁺.

Step 5: Synthesis of1-[4-Amino-2-(ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol

To a solution of1-[2-(ethoxymethyl)-9-methoxy-5-oxido-imidazo[4,5-c]quinolin-5-ium-1-yl]-2-methyl-propan-2-ol(150.00 mg, 434.29 μmol, 1.0 eq.) and NH₃.H₂O (543.64 mg, 4.34 mmol,597.41 μL, 28% purity, 10.0 eq.) in CHCl₃ (20.00 mL) was added TsCl(99.36 mg, 521.15 μmol, 1.2 eq.). The resulting mixture was stirred at20° C. for 0.5 h. The solvent was removed in vacuo. The residue waspurified with prep-HPLC (MeCN/H₂O as eluents, acidic condition). Afterlyophilization, the desired product of1-[4-amino-2-(ethoxymethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-ol(50.00 mg, 131.28 μmol, 30.23% yield, 100% purity, as HCl salt) wasobtained as a white solid. H NMR (400 MHz, CD₃OD) δ ppm: 7.63 (t, J=8.2Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 5.50 (s, 1H),5.21 (s, 1H), 4.76 (s, 1H), 4.55 (s, 1H), 4.09 (s, 3H), 3.59 (m, 2H),1.23-1.20 (m, 6H), 0.82 (m, 3H); ES-LCMS m/z: 345.3 [M+H]⁺

Example 2 Synthesis of2-(Ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinolin-4-amine

Step 1: Synthesis of2-(Ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinoline

To a solution of N⁴-isobutyl-5-methoxy-quinoline-3,4-diamine (100.00 mg,407.63 μmol, 1.0 eq.) and pyridine (322.44 mg, 4.08 mmol, 329.02 μL,10.0 eq.) in DCM (4.00 mL) was added 2-ethoxyacetyl chloride (99.91 mg,815.26 μmol, 2.0 eq.). The resulting mixture was stirred at 25° C. for 1h. The solvent was removed in vacuo. The residue was dissolved in NaOH(2 M, 4.95 mL, 24.3 eq.) and stirred at 100° C. for 5 h. The mixture wasdissolved in water (10 mL) and extracted with DCM (50 mL×2). Thecombined organic phase was washed with brine (20 mL), dried overanhydrous Na₂SO₄, filtered and concentrated in vacuo. The residue waspurified with prep-TLC (DCM/MeOH=15/1). The desired product of2-(ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinoline (80.00 mg,255.27 μmol, 62.62% yield) was obtained as a brown solid. ¹H NMR (400MHz, CDCl₃) δ ppm: 9.27 (s, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.60 (t, J=8.2Hz, 1H), 7.04 (d, J=8.0 Hz, 1H), 4.89 (s, 2H), 4.62 (br, s. 2H), 4.08(s, 3H), 3.65-3.59 (m, 2H), 2.11-2.02 (m, 1H), 1.26 (t, J=7.0 Hz, 3H),0.75-0.72 (m, 6H); ES-LCMS m/z: 314.3 [M+H]⁺.

Step 2:2-(Ethoxymethyl)-1-isobutyl-9-methoxy-5-oxido-imidazo[4,5-c]quinolin-5-ium

To a solution of2-(ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinoline (50.00 mg,159.55 μmol, 1.0 eq.) in DCM (5.00 mL) was added m-CPBA (48.59 mg,239.33 μmol, 85% purity, 1.5 eq.). The resulting mixture was stirred at25° C. for 0.5 h. DCM (40 mL) and water (10 mL) were added, and pH wasadjusted to 8 by addition of aqueous NaOH. The organic layer was thenseparated, washed with brine (10 mL), dried over Na₂SO₄ and filtered.The filtrate was concentrated in vacuo. The desired product of2-(ethoxymethyl)-1-isobutyl-9-methoxy-5-oxido-imidazo[4,5-c]quinolin-5-ium(50.00 mg, 151.80 μmol, 95.14% yield) was obtained as a yellow solid. ¹HNMR (400 MHz, CDCl₃) 67 ppm: 9.05 (s, 1H), 8.71 (d, J=8.8 Hz, 1H), 7.70(t, J=8.2 Hz, 1H), 7.17 (d, J=7.2 Hz, 1H), 4.56 (s, 2H), 4.44 (br, s.2H), 4.11 (s, 3H), 3.65-3.59 (m, 2H), 2.06-1.99 (m, 1H), 1.27 (t, J=7.0Hz, 3H), 0.76-0.72 (m, 6H); ES-LCMS m/z: 330.2 [M+H]⁺.

Step 3:2-(Ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinolin-4-amine

To a solution of2-(ethoxymethyl)-1-isobutyl-9-methoxy-5-oxido-imidazo[4,5-c]-quinolin-5-ium(50.00 mg, 151.80 μmol, 1.0 eq.) and NH₃.H₂O (190.27 mg, 1.52 mmol,209.09 μL, 28% purity, 10.0 eq.) in CHCl₃ (10.00 mL) was added TsCl(34.73 mg, 182.16 μmol, 1.2 eq.). The resulting mixture was stirred at25° C. for 0.5 h. The solvent was removed in vacuo. The residue waspurified with prep-HPLC (MeCN/H₂O as eluents, acidic condition). Afterlyophilization, the desired product of2-(ethoxymethyl)-1-isobutyl-9-methoxy-imidazo[4,5-c]quinolin-4-amine(30.00 mg, 78.31 μmol, 51.59% yield, 95.24% purity, as HCl salt) wasobtained as a white solid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.69 (t, J=8.2Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 4.87 (s, 2H),4.62 (br, s. 2H), 4.13 (s, 3H), 3.69-3.64 (m, 2H), 2.05-1.95 (m, 1H),1.27 (t, J=7.0 Hz, 3H), 0.80-0.75 (m, 6H); ES-LCMS m/z: 329.4 [M+H]⁺.

The following compounds were prepared using the same method as that inExample 1 or 2 using corresponding reagents.

1-[4-Amino-9-methoxy-2-(2-methoxyethyl)imidazo[4,5-c]quinolin-1-yl]-2-methyl-propan-2-olwas obtained as a white solid in 9.18% yield as a HCl salt with 98.5%purity. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.67 (t, J=8.4 Hz, 1H), 7.35 (d,J=8.4 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 5.60 (m, 1H), 4.48 (m, 1H), 4.14(s, 3H), 3.97 (m, 2H), 3.47-3.44 (m, 2H), 3.42 (s, 3H), 1.26 (s, 3H),0.89 (s, 3H); ES-LCMS m/z: 345.3 [M+H]⁺.

1-[4-Amino-2-(2-hydroxyethyl)-9-methoxy-imidazo[4,5-c]quinolin-1-yl]-2-methyl-pro-pan-2-olwas obtained as a white solid in 3.47% yield as a HCl salt with 100%purity. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.61 (t, J=8.4 Hz, 1H), 7.28 (d,J=8.0 Hz, 1H), 7.12 (d, J=7.6 Hz, 1H), 5.54 (m, 1H), 4.41 (m, 1H), 4.08(s, 3H), 4.07-4.05 (m, 2H), 3.27 (m, 2H), 1.20 (s, 3H), 0.85 (s, 3H);ES-LCMS m/z: 331.2 [M+H]⁺.

4-[[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-olwas obtained as a white solid in 40.57% yield as a HCl salt. ¹H NMR (400MHz, CD₃OD) δ ppm: 7.68 (t, J=8.4 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.15(d, J=8.4 Hz, 1H), 4.84 (s, 2H), 4.50 (t, J=6.0 Hz, 2H), 3.76-3.70 (m,2H), 2.19 (t, J=5.8 Hz, 2H), 1.43 (s, 6H), 1.31 (t, J=7.0 Hz, 3H);ES-LCMS m/z: 345.3 [M+H]⁺.

Example 3 Synthesis of2-(Ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinolin-4-amine

Step 1: Synthesis of 5-Isopentyloxy-3-nitro-quinolin-4-amine

To a solution of 4-amino-3-nitro-quinolin-5-ol (300.00 mg, 1.46 mmol,1.0 eq.), TBAB (470.66 mg, 1.46 mmol, 1.0 eq.) and KI (242.36 mg, 1.46mmol, 1.0 eq.) in NaOH (1 M, 4.38 mL, 3.0 eq.) was added a solution ofisopentyl 4-methylbenzenesulfonate (1.06 g, 4.38 mmol, 3.0 eq.) in DCM(4.00 mL). The resulting mixture was stirred at 20° C. for 40 h. Thereaction mixture was diluted with H₂O (10 mL) and extracted with DCM (30mL×2). The combined organic layers were washed with brine (10 mL), driedover Na₂SO₄, filtered and concentrated under reduced pressure to give aresidue. The residue was purified with column chromatography (PE toPE/EA=1/2). The desired product of5-isopentyloxy-3-nitro-quinolin-4-amine (140.00 mg, 508.54 μmol, 34.83%yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CDCl₃) δ ppm:9.33 (s, 1H), 9.25 (s, 1H), 9.10 (s, 1H), 7.66 (t, J=8.2 Hz, 1H), 7.57(d, J=8.4 Hz, 1H), 6.94 (d, J=7.6 Hz, 1H), 4.28 (t, J=6.2 Hz, 2H), 1.88(m, 3H), 1.05 (d, J=6.0 Hz, 6H); ES-LCMS m/z: 276.3 [M+H]⁺.

Step 2: Synthesis of 5-Isopentyloxyquinoline-3,4-diamine

To a solution of 5-isopentyloxy-3-nitro-quinolin-4-amine (140.00 mg,508.54 μmol, 1.0 eq.) in MeOH (50.00 mL) was added Raney-Ni (100.00 mg,1.17 mmol, 2.3 eq.) under N₂. The suspension was degassed under vacuumand purged with H₂ three times. The resulting mixture was stirred underH₂ (15 psi) at 20° C. for 2 h. The reaction mixture was filtered. Thefiltrate was concentrated in vacuo. The desired product of5-isopentyloxyquinoline-3,4-diamine (120.00 mg, 489.16 μmol, 96.19%yield) was obtained as a green solid. ¹H NMR (400 MHz, CD₃OD) δ ppm:8.01 (s, 1H), 7.53 (t, J=8.2 Hz, 1H), 7.27 (d, J=8.8 Hz, 1H), 6.96 (d,J=8.0 Hz, 1H), 4.30 (t, J=6.2 Hz, 2H), 1.89-1.87 (m, 3H), 1.04 (d, J=6.4Hz, 6H); ES-LCMS m/z: 246.3 [M+H]⁺.

Step 3: Synthesis of2-(Ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinoline

5-Isopentyloxyquinoline-3,4-diamine (110.00 mg, 448.39 μmol, 1.0 eq.),2-ethoxyacetic acid (1.21 g, 11.62 mmol, 1.10 mL, 25.9 eq.) and 4 Å MS(150.00 mg) were placed into a microwave tube. The sealed tube washeated at 130° C. for 1 h under microwave. The solid was filtered off.The filtrate was diluted with DCM (50 mL) and water (20 mL). The mixturewas adjusted to pH=7 with aqueous NaOH (1 M). The layers were separated.The organic phase was washed with brine (20 mL), dried over anhydrousNa₂SO₄, filtered and concentrated in vacuo. The residue was purifiedwith prep-TLC (DCM/MeOH=20/1). The desired product of2-(ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinoline (130.00 mg,414.82 μmol, 92.51% yield) was obtained as a yellow solid. ¹H NMR (400MHz, CD₃OD) δ ppm: 9.10 (s, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.66 (t, J=8.4Hz, 1H), 7.20 (d, J=7.6 Hz, 1H), 4.80 (s, 2H), 4.48 (t, J=6.6 Hz, 2H),3.73-3.68 (m, 2H), 1.95-1.88 (m, 3H), 1.29 (t, J=7.0 Hz, 3H), 1.05 (d,J=6.0 Hz, 6H); ES-LCMS m/z: 314.3 [M+H]⁺.

Step 4: Synthesis of2-(Ethoxymethyl)-9-isopentyloxy-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium

To a solution of2-(ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinoline (130.00 mg,414.82 μmol, 1.0 eq.) in DCM (30.00 mL) was added m-CPBA (126.33 mg,622.23 μmol, 85% purity, 1.5 eq.). The resulting mixture was stirred at20° C. for 0.5 h. The reaction mixture was diluted with DCM (20 mL) andwashed with saturated K₂CO₃ (10 mL) via extraction. The combined organiclayers were washed with brine (15 mL), dried over Na₂SO₄, filtered andconcentrated under reduced pressure. The desired product of2-(ethoxymethyl)-9-isopentyloxy-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium(130.00 mg, 394.67 μmol, 95.14% yield) was obtained as a brown solid. ¹HNMR (400 MHz, CD₃OD) δ ppm: 9.11 (s, 1H), 8.31 (d, J=8.4 Hz, 1H), 7.82(t, J=8.8 Hz, 1H), 7.41-7.38 (m, 1H), 4.88 (s, 2H), 4.54 (t, J=6.6 Hz,2H), 3.73-3.67 (m, 2H), 1.94-1.86 (m, 3H), 1.29 (t, J=7.0 Hz, 3H), 1.04(d, J=6.0 Hz, 6H); ES-LCMS m/z: 330.3 [M+H]⁺.

Step 5: Synthesis of2-(Ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinolin-4-amine

To a solution of2-(ethoxymethyl)-9-isopentyloxy-5-oxido-1H-imidazo[4,5-c]-quinolin-5-ium(130.00 mg, 394.67 μmol, 1.0 eq.) and NH₃.H₂O (494.04 mg, 3.95 mmol,542.90 μL, 28% purity, 10.0 eq.) in CHCl₃ (6.00 mL) was added TsCl(112.87 mg, 592.00 μmol, 1.5 eq.). The resulting mixture was stirred at25° C. for 0.5 h. The solvent was then removed in vacuo. The residue waspurified with prep-HPLC (MeCN/H₂O as eluents, acidic condition). Afterlyophilization, the desired product of2-(ethoxymethyl)-9-isopentyloxy-1H-imidazo[4,5-c]quinolin-4-amine (75.00mg, 196.61 μmol, 49.82% yield, 95.65% purity, as HCl salt) was obtainedas a white solid. ¹H NMR (400 MHz, CD₃OD) ≃ ppm: 7.68 (t, J=8.2 Hz, 1H),7.33 (d, J=8.4 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 4.86 (s, 2H), 4.51 (t,J=6.8 Hz, 2H), 3.75-3.70 (m, 2H), 1.94-1.86 (m, 3H), 1.31 (t, J=7.0 Hz,3H), 1.05 (d, J=6.4 Hz, 6H); ES-LCMS m/z: 329.3 [M+H]⁺.

The following compound was prepared using the same method as thatdescribed in Example 3 using corresponding reagents.

4-[[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]butan-2-olHCl salt was obtained in 20.06% yield with 100% purity as a white solid.¹H NMR (400 MHz, CD₃OD) δ ppm: 7.65 (t, J=8.4 Hz, 1H), 7.31 (d, J=8.0Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 4.79 (s, 2H), 4.54-4.53 (m, 1H),4.42-4.40 (m, 1H), 4.25-4.16 (m, 1H), 3.72-3.66 (m, 2H), 2.15-2.09 (m,2H), 1.35 (d, J=6.4 Hz, 3H), 1.27 (t, J=7.0 Hz, 3H); ES-LCMS m/z: 330.9[M+H]⁺.

Example 4 Synthesis of1-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propan-2-ol

Step 1: Synthesis of 1-[(4-Amino-3-nitro-5-quinolyl)oxy]propan-2-one

To a solution of 4-amino-3-nitro-quinolin-5-ol (1.00 g, 4.87 mmol, 1.0eq.), TBAB (1.57 g, 4.87 mmol, 1.0 eq.), KI (809.09 mg, 4.87 mmol, 1.0eq.) in NaOH (2 M, 7.31 mL, 3.0 eq.) was added acetonyl4-methylbenzenesulfonate (3.33 g, 14.61 mmol, 3.0 eq.) in DCM (8.00 mL)at 25° C. The mixture was stirred at 25° C. for 48 h. The reactionmixture was diluted with H₂O (20 mL) and extracted with DCM (50 mL×2).The combined organic layers were washed with brine (20 mL), dried overNa₂SO₄, filtered and concentrated under reduced pressure to give aresidue. The residue was purified with column chromatography (DCM toDCM/MeOH=20/1). The desired product of1-[(4-amino-3-nitro-5-quinolyl)oxy]propan-2-one (220.00 mg, 842.17 μmol,17.29% yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CDCl₃) δppm: 9.84 (br s, 1H), 9.41 (br s, 1H), 9.35 (s, 1H), 7.66-7.60 (m, 2H),6.80-6.77 (m, 1H), 4.92 (s, 2H), 2.37 (s, 3H); ES-LCMS m/z: 262.2[M+H]⁺.

Step 2: Synthesis of 1-[(3, 4-Diamino-5-quinolyl)oxy]propan-2-ol

To a solution of 1-[(4-amino-3-nitro-5-quinolyl)oxy]propan-2-one (220.00mg, 842.17 μmol, 1.0 eq.) in MeOH (100.00 mL) was added Raney-Ni (100.29mg, 1.17 mmol, 1.39 eq.) under N₂. The suspension was degassed undervacuum and purged with H₂ several times. The mixture was stirred underH₂ (15 psi) at 25° C. for 1 h. The solid was filtered off. The filtratewas concentrated in vacuo. The desired product of1-[(3,4-diamino-5-quinolyl)oxy]-propan-2-ol (160.00 mg, 685.90 μmol,81.44% yield) was obtained as a green solid. ¹H NMR (400 MHz, CD₃OD) δppm: 7.95 (s, 1H), 7.64-7.60 (m, 1H), 7.28-7.26 (m, 1H), 7.02-6.90 (m,1H), 4.32-4.29 (m, 2H), 4.07-4.04 (m, 1H), 1.33 (d, J=6.4 Hz, 3H);ES-LCMS m/z: 234.1 [M+H]⁺.

Step 3: Synthesis of1-[[2-(Ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]propan-2-ol

1-[(3,4-Diamino-5-quinolyl)oxy]propan-2-ol (150.00 mg, 643.03 μmol, 1.0eq.), 2-ethoxyacetic acid (1.10 g, 10.57 mmol, 1.00 mL, 16.4 eq.) and 4Å MS (50.00 mg) were placed into a microwave tube. The sealed tube washeated at 120° C. for 0.5 h under microwave. An aqueous solution of 3 MNaOH (10 mL) and THF (3 mL) were added into the reaction mixture. Theresulting mixture was stirred at 50° C. for 2 h. The mixture wasextracted with ethyl acetate (50 mL×3). The combined organic layers werewashed with saturated brine (10 mL), dried over anhydrous Na₂SO₄,filtered and concentrated under reduced pressure to give a residue. Theresidue was purified with prep-TLC (DCM/MeOH=15/1). The desired productof 1-[[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-propan-2-ol(23.00 mg, 76.33 μmol, 11.87% yield) was obtained as a yellow solid. ¹HNMR (400 MHz, CDCl₃) δ ppm: 11.52 (s, 1H), 9.20 (s, 1H), 7.81 (d, J=8.4Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 6.97 (d, J=7.6 Hz, 1H), 4.83 (s, 2H),4.42 (m, 1H), 4.32-4.28 (m, 1H), 4.02 (t, J=8.2 Hz, 1H), 3.64-3.61 (m,2H), 1.40 (m, 3H), 1.25 (m, 3H); ES-LCMS m/z: 302.2 [M+H]⁺.

Step 4: Synthesis of1-[[2-(Ethoxymethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy]propan-2-ol

To a mixture of1-[[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]propan-2-ol(23.00 mg, 76.33 μmol, 1.0 eq.) in DCM (8.00 mL) was added m-CPBA (30.99mg, 152.65 μmol, 85% purity, 2.0 eq.) in one portion at 25° C. Themixture was stirred at 25° C. for 1 h. The solvent was removed in vacuo.The crude product was used for the next step without furtherpurification. The crude product of1-[[2-(ethoxymethyl)-5-oxido-1H-imidazo[4,5-c]-quinolin-5-ium-9-yl]oxy]propan-2-ol(20.00 mg, 63.02 μmol, 82.57% yield) was obtained as a brown solid. ¹HNMR (400 MHz, CDCl₃) δ ppm: 9.17 (s, 1H), 8.39 (d, J=8.8 Hz, 1H),7.47-7.45 (m, 1H), 7.05-7.01 (m, 1H), 4.86 (s, 2H), 4.48 (m, 1H), 4.37(m, 1H), 4.06 (d, J=8.4 Hz, 1H), 3.74-3.71 (m, 2H), 1.47 (br d, J=6.4Hz, 3H), 1.35 (t, J=7.2 Hz, 3H); ES-LCMS m/z:=318.2 [M+H]⁺.

Step 5: Synthesis of1-[[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-propan-2-ol

To a mixture of1-[[2-(ethoxymethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy]propan-2-ol(20.00 mg, 63.02 μmol, 1.0 eq.) and NH₃.H₂O (78.89 mg, 630.24 μmol,86.69 μL, 28% purity, 10.0 eq.) in CHCl₃ (6.00 mL) was added TsCl (24.03mg, 126.05 μmol, 2.0 eq.) at 25° C. The mixture was stirred at 25° C.for 3 h. The reaction mixture was concentrated under reduced pressure toremove the solvent. The residue was purified with preparative HPLC(MeCN/H₂₀ as eluents, acidic condition). After lyophilization, thedesired product of1-[[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]propan-2-ol(4.68 mg, 13.26 μmol, 21.04% yield, as HCl salt) was obtained as a whitesolid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.66 (t, J=8.4 Hz, 1H), 7.35 (d,J=8.4 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 4.83 (s, 2H), 4.42-4.39 (m, 1H),4.36 (m, 1H), 4.18-4.16 (m, 1H), 3.71-3.68 (m, 2H), 1.36 (d, J=6.4 Hz,3H), 1.29 (t, J=7.2 Hz, 3H); ES-LCMS m/z: 317.2 [M+H]⁺.

Example 5 Synthesis of4-[[4-Amino--(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol

Step 1: Synthesis of4-[[2-(2-Methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol

To a solution of 4-[(3,4-diamino-5-quinolyl)oxy]-2-methyl-butan-2-ol(179.17 mg, 329.10 μmol, 1.0 eq.) and pyridine (260.32 mg, 3.29 mmol,265.63 μL, 10.0 eq.) in DCM (2.00 mL) was added 3-methoxypropanoylchloride (80.66 mg, 658.20 μmol, 2.0 eq.). The resulting mixture wasstirred at 25° C. for 16 h. The solvent was removed in vacuo. Theresidue was dissolved in NaOH (2 M, 4.00 mL, 24.3 eq.) and stirred at100° C. for 1 h. The mixture was diluted with water (10 mL) andextracted with DCM (50 mL×2). The combined organic phase was washed withbrine (30 mL), dried over Na₂SO₄, filtered and concentrated in vacuo.The residue was purified with prep-TLC (DCM/MeOH=15/1). The desiredproduct of4-[[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol(90.00 mg, 273.23 μmol, 83.02% yield) was obtained as a brown solid. ¹HNMR (400 MHz, CD₃OD) δ ppm: 9.08 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.65(t, J=8.0 Hz, 1H), 7.18 (d, J=7.2 Hz, 1H), 4.51 (t, J=6.0 Hz, 2H), 3.93(t, J=6.4 Hz, 2H), 3.42 (s, 3H), 3.33-3.28 (m, 2H), 2.23 (t, J=6.0 Hz,2H), 1.44 (s, 6H); ES-LCMS m/z: 330.3 [M+H]⁺.

Step 2: Synthesis of4-[[2-(2-Methoxyethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium-9yl]oxy]-2-methyl-butan-2-ol

To a solution of4-[[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol(90.00 mg, 273.23 μmol, 1.0 eq.) in DCM (10.00 mL) was added m-CPBA(83.21 mg, 409.85 μmol, 85% purity, 1.5 eq.). The resulting mixture wasstirred at 25° C. for 0.5 h. The solvent was removed in vacuo. Theresidue was purified with prep-TLC (DCM/MeOH=15/1). The desired productof4-[[2-(2-methoxyethyl)-5-oxido-1H-imidazo[4,5-c]-quinolin-5-ium-9-yl]oxy]-2-methyl-butan-2-ol(60.00 mg, 173.72 μmol, 63.58% yield) was obtained as a yellow solid. ¹HNMR (400 MHz, CDCl₃) δ ppm: 8.97 (s, 1H), 8.36 (d, J=8.8 Hz, 1H), 7.54(t, J=8.4 Hz, 1H), 6.94 (d, J=8.0 Hz, 1H), 4.38 (t, J=5.6 Hz, 2H), 3.81(t, J=6.2 Hz, 2H), 3.40 (s, 3H), 3.17 (t, J=6.0 Hz, 2H), 2.24 (t, J=5.6Hz, 2H), 1.48 (s, 6H); ES-LCMS m/z: 345.9 [M+H]⁺.

Step 3: Synthesis of4-[[4-Amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol

To a solution of4-[[2-(2-methoxyethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy]-2-methyl-butan-2-ol(60.00 mg, 173.72 μmol, 1.0 eq.) and NH₃.H₂O (217.81 mg, 1.74 mmol,239.35 μL, 28% purity, 10.0 eq.) in CHCl₃ (6.00 mL) was added TsCl(66.24 mg, 347.44 μmol, 2.0 eq.). The resulting mixture was stirred at25° C. for 0.5 h. The solvent was removed in vacuo. The residue waspurified with prep-HPLC (MeCN/H₂O as eluents, acidic condition). Afterlyophilization, the desired product of4-[[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl]oxy]-2-methyl-butan-2-ol(24.95 mg, 63.20 μmol, 36.38% yield, 96.48% purity, as HCl salt) wasobtained as a white solid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.66 (t, J=8.2Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 4.49 (t, J=6.0Hz, 2H), 3.93 (t, J=6.6 Hz, 2H), 3.42 (s, 3H), 3.26 (t, J=6.2 Hz, 2H),2.19 (t, J=5.8 Hz, 2H), 1.43 (s, 6H); ES-LCMS m/z: 345.3 1M+H₊.

Example 6 Synthesis of4-[4-Amino-2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

Step 1: Synthesis of 4-(methylamino)-3-nitro-quinolin-5-ol

To a solution of 5-methoxy-N-methyl-3-nitro-quinolin-4-amine (300.00 mg,1.29 mmol, 1.0 eq.) in DCM (15.00 mL) was added BBr₃ (1.62 g, 6.45 mmol,621.48 μL, 5.0 eq.) dropwise at −78° C. The resulting mixture wasstirred at 60° C. for 2 h. The mixture was added to MeOH (100 mL)dropwise at −30° C. The solvent was removed in vacuo. The desiredproduct of 4-(methylamino)-3-nitro-quinolin-5-ol (300.00 mg, crude) wasobtained as a brown solid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 9.22 (s, 1H),7.79 (m, 1H), 7.33 (m, 1H), 7.15-7.13 (m, 1H), 3.08 (s, 3H); ES-LCMSm/z: 220.2 M+H⁺.

Step 2: Synthesis of2-methyl-4[[4-(methylamino)-3-nitro-5-quinolyl]oxy]butan-2-ol

To a solution of 4-(methylamino)-3-nitro-quinolin-5-ol (250.00 mg, 1.14mmol, 1.0 eq.), TBAB (367.67 mg, 1.14 mmol, 1.0 eq.) and KI (189.32 mg,1.14 mmol, 1.0 eq.) in NaOH (2 M, 1.71 mL, 3.0 eq.) was added a solutionof (3-hydroxy-3-methyl-butyl)4-methylbenzenesulfonate (883.49 mg, 3.42mmol, 3.0 eq.) in DCM (3.00 mL). The resulting mixture was stirred at25° C. for 64 h. The reaction mixture was diluted with H₂O (10 mL) andextracted with DCM (30 mL×2). The combined organic layers were washedwith brine (10 mL), dried over Na₂SO₄, filtered and concentrated underreduced pressure to give a residue. The residue was purified with columnchromatography (DCM to DCM/MeOH=20/1). The desired product of2-methyl-4[[4-(methylamino)-3-nitro-5-quinolyl]oxy]butan-2-ol (100.00mg, 327.51 μmol, 28.73% yield) was obtained as a yellow solid. ¹H NMR(400 MHz, CDCl₃) δ ppm: 9.36 (s, 1H), 9.02 (s, 1H), 7.61-7.55 (m, 2H),6.91 (d, J=6.8 Hz, 1H), 4.36 (t, J=5.8 Hz, 2H), 2.84 (d, J=5.2 Hz, 3H),2.13 (t, J=5.8 Hz, 2H), 1.41 (s, 6H); ES-LCMS m/z: 306.0 [M+H]⁺.

Step 3: Synthesis of4-[[3-Amino-4-(methylamino)-5-quinolyl]oxy]-2-methyl-butan-2-ol

To a solution of2-methyl-4-[[4-(methylamino)-3-nitro-5-quinolyl]oxy]butan-2-ol (100.00mg, 327.51 μmol, 1.0 eq.) in MeOH (50.00 mL) was added Raney-Ni (100.00mg, 1.17 mmol, 3.6 eq.) under N₂. The suspension was degassed undervacuum and purged with H₂ several times. The mixture was stirred underH₂ (15 psi) at 25° C. for 1 h. The mixture was filtered. The filtratewas concentrated in vacuo. The desired product of4-[[3-amino-4-(methylamino)-5-quinolyl]oxy]-2-methyl-butan-2-ol (80.00mg, 290.54 μmol, 88.71% yield) was obtained as a green solid. ¹H NMR(400 MHz, CD₃OD) δ ppm: 8.07 (s, 1H), 7.44 (t, J=8.0 Hz, 1H), 7.29 (d,J=8.4 Hz, 1H), 6.95 (d, J=7.6 Hz, 1H), 4.35 (t, J=6.4 Hz, 2H), 3.19 (d,J=10.4 Hz, 3H), 2.10 (d, J=6.4 Hz, 2H), 1.33 (s, 6H); ES-LCMS m/z: 276.3[M+H]⁺.

Step 4: Synthesis of4-[2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

4-[[3-Amino-4-(methylamino)-5-quinolyl]oxy]-2-methyl-butan-2-ol (70.00mg, 254.22 μmol, 1.0 eq.), 2-ethoxyacetic acid (1.65 g, 15.85 mmol, 1.50mL, 62.4 eq.) and 4 Å MS (100.00 mg) were placed into a microwave tube.The sealed tube was heated at 120° C. for 30 minutes under microwave.The mixture was filtered. The filtrate was diluted with DCM (50 mL) andwater (10 mL) and was adjusted to pH=7 by aqueous NaOH (2 M). Theorganic layer was separated and washed with brine (10 mL), dried withanhydrous Na₂SO₄, filtered and concentrated in vacuo. The crude productwas purified with prep-TLC (DCM/MeOH=15/1). The desired product of4-[2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol(20.00 mg, 58.24 μmol, 22.91% yield) was obtained as a yellow solid. ¹HNMR (400 MHz, CDCl₃) δ ppm: 9.25 (s, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.59(t, J=8.2 Hz, 1H), 7.10 (d, J=7.2 Hz, 1H), 4.89 (s, 2H), 4.48 (t, J=7.6Hz, 2H), 4.32 (s, 3H), 3.66-3.61 (m, 2H), 2.20 (t, J=7.6 Hz, 2H), 1.38(s, 6H), 1.26 (m, 3H); ES-LCMS m/z: 344.3 [M+H]⁺.

Step 5: Synthesis of4-[2-(Ethoxymethyl)-1-methyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol

To a solution of4-[2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]-oxy-2-methyl-butan-2-ol(20.00 mg, 58.24 μmol, 1.0 eq.) in DCM (5.00 mL) was added m-CPBA (23.65mg, 116.48 μmol, 85% purity, 2.0 eq.). The resulting mixture was stirredat 25° C. for 0.5 h. The solvent was removed in vacuo. The residue waspurified with prep-TLC (DCM/MeOH=10/1). The desired product of4-[2-(ethoxymethyl)-1-methyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol(20.00 mg, crude) was obtained as a white solid. ¹H NMR (400 MHz, CDCl₃)δ ppm: 9.28 (s, 1H), 8.70 (d, J=8.8 Hz, 1H), 7.71 (t, J=8.2 Hz, 1H),7.22 (d, J=8.0 Hz, 1H), 4.86 (s, 2H), 4.52-4.48 (m, 2H), 4.28 (s, 3H),3.67-3.61 (m, 2H), 2.23-2.16 (m, 2H), 1.35 (s, 6H), 1.29-1.27 (m, 3H);ES-LCMS m/z: 360.3 [M+H]⁺.

Step 6: Synthesis of4-[4-Amino-2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

To a solution of4-[2-(ethoxymethyl)-1-methyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol(20.00 mg, 55.65 μmol, 1.0 eq.) and NH₃.H₂O (69.66 mg, 556.45 μmol,76.54 μL, 28% purity, 10.0 eq.) in CHCl₃ (2.00 mL) was added TsCl (15.91mg, 83.47 μmol, 1.5 eq.). The resulting mixture was stirred at 25° C.for 0.5 h. The solvent was removed in vacuo. The residue was purifiedwith prep-HPLC (MeCN/H₂O as eluents, acidic condition). Afterlyophilization, the desired product of4-[4-amino-2-(ethoxymethyl)-1-methyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol(6.00 mg, 15.19 μmol, 27.30% yield, as a HCl salt) was obtained as awhite solid: ¹H NMR (400MHz, CD₃OD) δ ppm: 7.65 (t, J=8.2 Hz, 1H), 7.31(d, J=8.4 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 4.85 (s, 2H), 4.48 (t, J=7.8Hz, 2H), 4.26 (s, 3H), 3.68-3.63 (m, 2H), 2.16 (t, J=7.8 Hz, 2H), 1.31(s, 6H), 1.26 (t, J=6.8 Hz, 3H); ES-LCMS m/z: 359.3 [M+H]⁺.

The following compound was prepared in a similar way as that describedin Examples 5 and 6 using corresponding reagents.

2-(Ethoxymethyl)-9-(2-isopropoxyethoxy)-1H-imidazo[4,5-c]quinolin-4-aminewas obtained in 40.79% yield with 100% purity as a HCl salt as a whitesolid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.63 (t, J=8.2 Hz, 1H), 7.30 (d,J=8.4 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 4.79 (s, 2H), 4.54-4.51 (m, 2H),3.94-3.91 (m, 2H), 3.75-3.69 (m, 1H), 3.66-3.64 (m, 2H), 1.24 (t, J=7.0Hz, 3H), 1.15 (d, J=6.0 Hz, 6H) ; ES-LCMS m/z: 345.3 [M+H].

Example 7 Synthesis of4-[4-Amino-2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

Step 1: Synthesis of 3-Amino-4-(isobutylamino)quinolin-5-ol

To a solution of N⁴-isobutyl-5-methoxy-quinoline-3,4-diamine (450.00 mg,1.83 mmol, 1.0 eq.) in DCM (30.00 mL) was added BBr₃ (2.30 g, 9.17 mmol,883.73 μL, 5.0 eq.) dropwise at −78° C. The resulting mixture wasstirred at 60° C. for 2 h. The mixture was added to Me0H (100 mL)dropwise at −30° C. The solvent was removed in vacuo. The desiredproduct of 3-amino-4-(isobutylamino) quinolin-5-ol (500.00 mg, 1.64mmol, 89.81% yield, as 2HCl salt) was obtained as a brown solid. ¹H NMR(400 MHz, CD₃OD) δ ppm: 8.19 (s, 1H), 7.65 (t, J=8.2 Hz, 1H), 7.24 (d,J=8.4 Hz, 1H), 6.97 (d, J=7.2 Hz, 1H), 3.80 (d, J=6.4 Hz, 2H), 2.07-2.02(m, 1H), 1.10 (d, J=6.4 Hz, 6H); ES-LCMS m/z: 232.3 [M+H]⁺.

Step 2: Synthesis of2-(Ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-ol

To a solution of 3-amino-4-(isobutylamino)quinolin-5-ol (450.00 mg, 1.48mmol, 1.0 eq., as 2HCl salt) in Pyridine (4.90 g, 61.95 mmol, 5.0 mL,41.9 eq.) was added 2-ethoxyacetyl chloride (271.92 mg, 2.22 mmol, 1.5eq.). The resulting mixture was stirred at 25° C. for 1 h. The solventwas removed in vacuo. The residue was dissolved in NaOH (2 M, 7.40 mmol,3.0 mL, 5.0 eq.) and stirred at 100° C. for 2 h. The mixture waspartitioned between DCM (40 mL) and water (10 mL). The organic layer wasseparated, washed with brine (10 mL), dried over Na₂SO₄, filtered andconcentrated in vacuo. The residue was purified with columnchromatography (DCM to DCM/MeOH=10/1). The desired product of2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-ol (100.00 mg,334.03 μmol, 22.58% yield) was obtained as a red solid. ¹H NMR (400 MHz,CD₃OD) δ ppm: 9.06 (s, 1H), 7.69-7.67 (m, 1H), 7.56 (t, J=8.0 Hz, 1H),7.11-7.08 (m, 1H), 4.89 (s, 2H), 4.65-4.63 (m. 2H), 3.68-3.62 (m, 2H),2.24-2.16 (m, 1H), 1.26 (t, J=7.0 Hz, 3H), 0.79-0.76 (m, 6H); ES-LCMSm/z: 300.3 [M+H]⁺.

Step 3: Synthesis of4-[2-(Ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

To a solution of 2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-ol(60.00 mg, 200.42 μmol, 1.0 eq.), TBAB (64.61 mg, 200.42 μmol, 1.0 eq.)and KI (33.27 mg, 200.42 μmol, 1.0 eq.) in NaOH (2 M, 300.63 μL, 3.0eq.) was added a solution of(3-hydroxy-3-methyl-butyl)4-methylbenzenesulfonate (155.32 mg, 601.26μmol, 3.0 eq.) in DCM (3.00 mL). The resulting mixture was stirred at25° C. for 64 h. The reaction mixture was diluted with H₂O (20 mL) andextracted with DCM (50 mL×2). The combined organic layers were washedwith brine (20 mL), dried over Na₂SO₄, filtered and concentrated underreduced pressure to give a residue. The residue was purified with columnchromatography (DCM to DCM/MeOH=10/1). The desired product of4-[2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol (60.00 mg, 155.64 μmol, 77.66%yield) was obtained as a red solid. ¹H NMR (400 MHz, CDCl₃) δ ppm: 9.26(s, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.59 (t, J=8.2 Hz, 1H), 7.09 (d, J=7.2Hz, 1H), 4.88 (s, 2H), 4.68 (br, s. 2H), 4.48 (t, J=7.4 Hz, 2H),3.65-3.59 (m, 2H), 2.19 (t, J=7.6 Hz, 2H), 2.06-2.02 (m, 1H), 1.34 (s,6H), 1.28-1.24(m, 3H), 0.66 (d, J=6.0 Hz, 6H); ES-LCMS m/z: 386.4[M+H]⁺.

Step 4: Synthesis of4-[2-(Ethoxymethyl)-1-isobutyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol

To a solution of4-[2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol(60.00 mg, 155.64 μmol, 1.0 eq.) in DCM (10.00 mL) was added m-CPBA(47.40 mg, 233.46 μmol, 85% purity, 1.5 eq.). The resulting mixture wasstirred at 25° C. for 0.5 h. The solvent was removed in vacuo. Theresidue was purified with prep-TLC (DCM/MeOH=10/1). The desired productof 4-[2-(ethoxymethyl)-1-isobutyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol (50.00 mg, 124.53 μmol,80.01% yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CDCl₃) δppm: 9.07 (s, 1H), 8.68 (d, J=8.0 Hz, 1H), 7.68 (t, J=8.4 Hz, 1H), 7.22(d, J=8.0 Hz, 1H), 4.84 (s, 2H), 4.61 (br, s. 2H), 4.51 (t, J=7.8 Hz,2H), 3.65-3.59 (m, 2H), 2.19 (t, J=7.6 Hz, 2H), 1.99-1.94 (m, 1H), 1.35(s, 6H), 1.29-1.27 (m, 3H), 0.67 (d, J=6.0 Hz, 6H); ES-LCMS m/z: 402.4[M+H]⁺.

Step 5: Synthesis of4-[4-Amino-2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol

To a solution of4-[2-(ethoxymethyl)-1-isobutyl-5-oxido-imidazo[4,5-c]quinolin-5-ium-9-yl]oxy-2-methyl-butan-2-ol(50.00 mg, 124.53 μmol, 1.0 eq.) and NH₃.H₂O (155.89 mg, 1.25 mmol,171.31 μL, 28% purity, 10.0 eq.) in CHCl₃ (5.00 mL) was added TsCl(28.49 mg, 149.44 μmol, 1.2 eq.). The resulting mixture was stirred at25° C. for 0.5 h. The solvent was removed in vacuo. The residue waspurified with prep-HPLC (MeCN/HO as eluents, acidic condition). Afterlyophilization, the desired product of4-[4-amino-2-(ethoxymethyl)-1-isobutyl-imidazo[4,5-c]quinolin-9-yl]oxy-2-methyl-butan-2-ol(26.50 mg, 60.38 μmol, 48.48% yield, 99.56% purity, as a HCl salt) wasobtained as a white solid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 7.69 (t, J=8.2Hz, 1H), 7.34 (t, J=8.0 Hz, 1H), 7.22 (d, J=8.4 Hz, 1H), 4.87 (s, 2H),4.71 (br, s. 2H), 4.53 (t, J=7.6 Hz, 1H), 3.69-3.63 (m, 2H), 2.18 (t,J=7.6 Hz, 2H), 2.02-1.97 (m, 1H), 1.29 (s, 6H), 1.26 (t, J=7.0 Hz, 3H),0.74 (d, J=4.2 Hz, 6H); ES-LCMS m/z: 401.4 [M+H]⁺.

Example 8 Preparation of Intermediates Intermediate 1:4-Chloro-5-methoxy-3-nitro-quinoline

Step 1: Synthesis of 2-methoxy-6-[[(E)-2-nitrovinyl]amino]benzoic acid

To a solution of NaOH (40.20 g, 1.01 mol, 3.4 eq.) in water (100 mL) wasadded CH₃NO₂ (23.73 g, 388.84 mmol, 21.00 mL, 1.3 eq.) at 0° C. Themixture was warmed to 40° C. and additional amount of CH₃NO₂ (23.73 g,388.84 mmol, 21.00 mL, 1.3 eq.) was added slowly at 40° C. Thistemperature was maintained until all solids dissolved and a clear redsolution was obtained. The solution was cooled to 30° C., poured into300 g of chipped ice, and acidified with concentrated HCl (100 mL). Themixture was immediately added to a solution of 2-amino-6-methoxy-benzoicacid (50.00 g, 299.11 mmol, 1.0 eq.) and conc. HCl (35 mL) in water(1400 mL). The solution was allowed to stir at 20° C. for 16 h. Themixture was filtered. The cake was washed with water (300 mL×3), anddried in vacuo. The desired product of2-methoxy-6-[[(E)-2-nitrovinyl]amino]benzoic acid (67.00 g, 281.28 mmol,94.04% yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CD₃OD) δppm: 7.70 (d, J=6.0 Hz, 1H), 7.51 (t, J=8.4 Hz, 1H), 7.11 (d, J=8.4 Hz,1H), 6.93 (d, J=8.4 Hz, 1H), 6.68 (d, J=6.0 Hz, 1H), 3.89 (d, J=4.4 Hz,3H); ES-LCMS m/z: 261.1 [M+Na]⁺.

Step 2: Synthesis of 5-methoxy-3-nitro-quinolin-4-ol

A solution of 2-methoxy-6-[[(E)-2-nitrovinyl]amino]benzoic acid (56.00g, 235.10 mmol, 1.0 eq.) in Ac₂O (300.00 mL) was heated at 105° C. for0.5 h, and a clear solution was obtained. AcOK (27.69 g, 282.12 mmol,1.2 eq.) was added. The resulting mixture was stirred at 105° C. for 2h. The mixture was filtered. The cake was washed with acetic acid (30mL×2) and water (100 mL×3). The cake was dried on oil pump. The desiredproduct of 5-methoxy-3-nitro-quinolin-4-ol (19.00 g, 86.29 mmol, 36.70%yield) was obtained as an off-white solid. ¹H NMR (400 MHz, DMSO-d₆) δppm: 12.59 (s, 1H), 8.96 (s, 1H), 7.62 (t, J=8.2 Hz, 1H), 7.16 (d, J=8.0Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 3.83 (s, 3H); ES-LCMS m/z: 221.2[M+H]⁺.

Step 3: Synthesis of 4-chloro-5-methoxy-3-nitro-quinoline

To a suspension of 5-methoxy-3-nitro-quinolin-4-ol (2.00 g, 9.08 mmol,1.0 eq.) in SOCl₂ (8.20 g, 68.92 mmol, 5.00 mL, 7.6 eq.) was added DMF(66.39 mg, 908.35 μmol, 69.89 μL, 0.1 eq.). The resulting mixture wasstirred at 80° C. for 4 h. The solvent was removed in vacuo. The desiredproduct of 4-chloro-5-methoxy-3-nitro-quinoline (2.10 g, 8.80 mmol,96.92% yield) was obtained as a brown solid. ¹H NMR (400 MHz, CDCl₃) δppm: 9.12 (s, 1H), 8.08 (t, J=8.8 Hz, 1H), 7.96-7.92 (m, 1H), 7.20 (d,J=8.4 Hz, 1H), 4.08 (s, 3H); ES-LCMS m/z: 239.2 [M+H]⁺.

Intermediate 2: 4-Amino-3-nitro-quinolin-5-ol

Step 1: Synthesis of 5-methoxy-3-nitro-quinolin-4-amine

A solution of 4-chloro-5-methoxy-3-nitro-quinoline (5.28 g, 22.13 mmol,1.0 eq.) in THF (50 mL) was added to NH₃.H₂O (91.00 g, 726.96 mmol,100.00 mL, 28% purity, 32.9 eq.) in THF (100 mL) dropwise at 0° C. Themixture was stirred at 25° C. for 2 h. The reaction mixture wasfiltered. The residue was washed with H₂O (50 mL×3) and dried in vacuo.The desired product of 5-methoxy-3-nitro-quinolin-4-amine (4.83 g, 22.03mmol, 99.55% yield) was obtained as a yellow solid. ¹H NMR (400 MHz,CD₃OD) δ ppm: 9.17 (s, 1H), 7.75 (t, J=8.4 Hz, 1H), 7.46 (d, J=8.4 Hz,1H), 7.15 (d, J=8.0 Hz, 1H), 4.13 (s, 3H); ES-LCMS m/z: 220.2 [M+H]⁺.

Step 2: Synthesis of 4-amino-3-nitro-quinolin-5-ol

To a solution of 5-methoxy-3-nitro-quinolin-4-amine (2.00 g, 9.12 mmol,1.0 eq.) in DCM (100.00 mL) was added BBr₃ (22.86 g, 91.20 mmol, 8.79mL, 10.0 eq.) dropwise at −78° C. The reaction mixture was stirred at60° C. for 16 h. The reaction mixture was added to MeOH (200 mL) at −30°C., and then concentrated under reduced pressure to give a residue. Theresidue was suspended in DCM and filtered. The cake was dried in vacuo.The desired product of 4-amino-3-nitro-quinolin-5-ol (2.53 g, crude) wasobtained as a green solid. ¹H NMR (400 MHz, CD₃OD) δ ppm: 9.41 (s, 1H),7.83 (t, J=8.4 Hz, 1H), 7.33 (d, J=8.4 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H);ES-LCMS m/z: 206.2 [M+H]⁺.

Intermediate 3: N⁴-Isobutyl-5-methoxy-quinoline-3,4-diamine

Step 1: Synthesis of N-isobutyl-5-methoxy-3-nitro-quinolin-4-amine

To a solution of 2-methylpropan-1-amine (612.91 mg, 8.38 mmol, 828.26μL, 2.0 eq.) and Et₃N (2.12 g, 20.95 mmol, 2.90 mL, 5.0 eq.) in DCM(50.00 mL) was added 4-chloro-5-methoxy-3-nitro-quinoline (1.00 g, 4.19mmol, 1.0 eq.). The resulting mixture was stirred at 25° C. for 0.5 h.The reaction mixture was washed with water (30 mL) and brine (30 mL) viaextraction. The organic phase was dried over anhydrous Na₂SO₄, filteredand concentrated in vacuo. The residue was purified with columnchromatography (PE to PE/EtOAc=1/1). The desired product ofN-isobutyl-5-methoxy-3-nitro-quinolin-4-amine (1.00 g, 3.63 mmol, 86.69%yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CD₃OD) δ ppm:8.85 (s, 1H), 7.70 (t, J=8.2 Hz, 1H), 7.47 (d, J=7.6 Hz, 1H), 7.16 (d,J=8.0 Hz, 1H), 4.14 (s, 3H), 2.85 (d, J=6.4 Hz, 2H), 2.04-1.94 (m, 1H),1.00 (d, J=6.8 Hz, 6H); ES-LCMS m/z: 276.2 [M+H]⁺.

Step 2: Synthesis of N⁴-isobutyl-5-methoxy-quinoline-3,4-diamine

To a solution of N-isobutyl-5-methoxy-3-nitro-quinolin-4-amine (300.00mg, 1.09 mmol, 1.0 eq.) in MeOH (50.00 mL) was added Raney-Ni (100.00mg, 1.17 mmol, 1.1 eq.) under N₂. The suspension was degassed undervacuum and purged with H₂ several times. The mixture was stirred underH₂ (15 psi) at 25° C. for 1 h. The reaction mixture was filtered. Thefiltrate was concentrated in vacuo. The desired product ofN⁴-isobutyl-5-methoxy-quinoline-3,4-diamine (250.00 mg, 1.02 mmol,93.49% yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CD₃OD) δppm: 8.28 (s, 1H), 7.42-7.40 (m, 1H), 7.33 (t, J=8.2 Hz, 1H), 6.91 (d,J=7.6 Hz, 1H), 4.03 (s, 3H), 3.08 (d, J=6.8 Hz, 2H), 1.90-1.80 (m, 1H),1.02 (d, J=6.8 Hz, 6H); ES-LCMS m/z: 246.3 [M+H]⁺.

Intermediate 4: 4-[3,4-Diamino-5-quinolyl)oxy]-2-methyl-butan-2-ol

Step 1: Synthesis of4-[(4-amino-3-nitro-5-quinolyl)oxy]-2-methyl-butan-2-ol

To a solution of 4-amino-3-nitro-quinolin-5-ol (1.50 g, 7.31 mmol, 1.0eq.), TBAB (2.36 g, 7.31 mmol, 1.0 eq.) and KI (405.04 mg, 2.44 mmol,1.0 eq.) in NaOH (2 M, 3.66 mL, 3.0 eq.) was added a solution of(3-hydroxy-3-methyl-butyl)4-methylbenzenesulfonate (5.67 g, 21.93 mmol,3.0 eq.) in DCM (15.00 mL). The resulting mixture was stirred at 25° C.for 64 h. The reaction mixture was diluted with H₂O (10 mL) andextracted with DCM (50 mL×2). The combined organic layers were washedwith brine (10 mL), dried over anhydrous Na₂SO₄, filtered andconcentrated under reduced pressure to give a residue. The residue waspurified with column chromatography (SiO₂, DCM/MeOH=100/1 to 20/1). Thedesired product of4-[4-amino-3-nitro-5-quinolyl)oxy]-2-methyl-butan-2-ol (646.00 mg, 2.22mmol, 30.34% yield) was obtained as a yellow solid. ¹H NMR (400 MHz,CDCl₃) δ ppm: 9.59 (br s, 1H), 9.29 (s, 1H), 9.22 (br s, 1H), 7.63 (t,J=8.2 Hz, 1H), 7.54 (dd, J=8.4, 0.8 Hz, 1H), 6.92 (d, J=7.6 Hz, 1H),4.38 (t, J=6.2 Hz, 2H), 2.14 (t, J=6.2 Hz, 2H), 1.41 (s, 6H); ES-LCMSm/z: 292.3 [M+H]⁺.

Step 2: Synthesis of 4-[(3,4-diamino-5-quinolyl)oxy]-2-methyl-butan-2-ol

To a solution of 4-[4-amino-3-nitro-5-quinolyl)oxy]-2-methyl-butan-2-ol(640.00 mg, 2.20 mmol, 1.0 eq.) in MeOH (150.00 mL) was added Raney-Ni(200.00 mg, 2.33 mmol, 1.1 eq.) under N₂. The suspension was degassedunder vacuum and purged with H₂ several times. The mixture was stirredunder H₂ (15 psi) at 25° C. for 1 h. The reaction mixture was filtered.The filtrate was concentrated under reduced pressure to give a residue.The product was directly used in the next step without furtherpurification. The desired crude product of 4-[(3,4-diamino-5-quinolyl)oxy]-2-methyl-butan-2-ol (570.00 mg, 2.18 mmol, 99.15% yield) wasobtained as a black brown solid. ¹H NMR (400 MHz, CDCl₃) δ ppm: 8.24 (s,1H), 7.47 (d, J=8.4 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 6.68 (d, J=7.6 Hz,1H), 5.89 (br s, 2H), 4.28 (t, J=6.4 Hz, 2H), 2.11 (t, J=6.4 Hz, 2H),1.36 (s, 6H); ES-LCMS m/z: 262.2 [M+H].

Intermediate 5: 5-Methoxy-N-methyl-3-nitro-quinolin-4-amine

A solution of 4-chloro-5-methoxy-3-nitro-quinoline (1.00 g, 4.19 mmol,1.0 eq.) in DCM (30.00 mL) was added to MeNH₂ (2 M in THF, 40.00 mL,19.1 eq.). The mixture was stirred at 25° C. for 2 h. The mixture wasconcentrated to give a residue. The residue was purified with columnchromatography (SiO₂, DCM/MeOH=50/1 to 20/1). The desired product of5-methoxy-N-methyl-3-nitro-quinolin-4-amine (400.00 mg, 1.72 mmol,40.93% yield) was obtained as a yellow solid. ¹H NMR (400 MHz, CDCl₃) δppm: 9.03 (s, 1H), 8.79 (s, 1H), 7.62-7.60 (m, 2H), 6.94-6.92 (m, 1H),4.09 (s, 3H), 2.94 (d, J=5.6 Hz, 3H); ES-LCMS m/z: 234.0 [M+H]⁺.

Intermediate 6: 2-Ethoxyacetyl Chloride

To a solution of 2-ethoxyacetic acid (1.00 g, 9.61 mmol, 909.09 μL, 1.0eq.) and catalytic amount of DMF (10.00 mg, 136.82 μmol, 10.53 μL, 0.01eq.) in DCM (30.00 mL) was added oxalyl chloride (1.83 g, 14.41 mmol,1.26 mL, 1.5 eq.) at 0° C. The resulting mixture was stirred at 25° C.for 2 h. The reaction mixture was concentrated under reduced pressure toremove the solvent. 2-Ethoxyacetyl chloride (900.00 mg, 7.34 mmol,76.42% yield) was obtained as yellow oil.

Intermediate 7: 3-Methoxypropanoyl Chloride

3-Methoxypropanoyl chloride was prepared in the same way as intermediate6 using the corresponding starting material of 3-methoxypropanoic acidin 84.9% yield as yellow oil.

Intermediate 8: (3-Hydroxy-3-methyl-butyl) 4-methylbenzenesulfonate

To a solution of 3-methylbutane-1,3-diol (10.00 g, 96.02 mmol, 10.20 mL,1.0 eq.), Et₃N (14.57 g, 144.03 mmol, 19.96 mL, 1.5 eq.) and DMAP (14.08g, 115.22 mmol, 1.2 eq.) in DCM (200.00 mL) was added a solution of TsCl(17.39 g, 91.22 mmol, 0.95 eq) in DCM (100 mL) dropwise at 0° C. Theresulting mixture was stirred at 0° C. for 1 h. The mixture was adjustedto pH=6 with citric acid. The organic layer was separated and washedwith brine (100 mL), dried over anhydrous Na₂SO₄, filtered andconcentrated in vacuo.(3-Hydroxy-3-methyl-butyl)4-methylbenzenesulfonate (19.80 g, 76.65 mmol,79.83% yield) was obtained as a colorless oil. ¹H NMR (400 MHz, CDCl₃) δppm: 7.80-7.78 (m, 2H), 7.34 (d, J=8.0 Hz, 2H), 4.22-4.19 (m, 2H), 2.45(s, 3H), 1.87-1.84 (m, 2H), 1.21 (d, J=1.2 Hz, 6H); ES-LCMS m/z: 276.2[M+H₂O]⁺.

Intermediate 9: Isopentyl 4-methylbenzenesulfonate

Isopentyl 4-methylbenzenesulfonate was prepared in a similar way asintermediate 8 using the corresponding starting material of3-methylbutan-1-ol and purified with silica gel chromatography(PE/EA=20/1 to 10/1) to give 72.76% isolated yield as a yellow oil. ¹HNMR (400 MHz, CDCl₃) δ ppm: 7.81-7.79 (m, 2H), 7.35 (d, J=8.0 Hz, 2H),4.06 (t, J=6.6 Hz, 2H), 2.46 (s, 3H), 1.70-1.67 (m, 1H), 1.57-1.51 (m,2H), 0.88-0.84 (m, 6H); ES-LCMS m/z: 264.9 [M+Na]⁺.

Intermediate 10: 2-Isopropoxyethyl 4-methylbenzenesulfonate

2-Isopropoxyethyl 4-methylbenzenesulfonate was prepared in a similar wayas intermediate 8 using the corresponding starting material of2-isopropoxyethanol in 81.44% yield as a colorless oil. ¹H NMR (400 MHz,CDCl₃) δ ppm: 7.80 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.4 Hz, 2H), 4.14-4.11(m, 2H), 3.60-3.58 (m, 2H), 3.55-3.54 (m, 1H), 2.44 (s, 3H), 1.08 (d,J=6.0 Hz, 6H); ES-LCMS m/z: 259.3 [M+H]⁺.

Intermediate 11: 3-Hydroxybutyl 4-methylbenzenesulfonate

3-Hydroxybutyl 4-methylbenzenesulfonate was prepared in a similar way asintermediate 8 using the corresponding starting material ofbutane-1,3-diol in 59.04% yield as a colorless oil. ¹H NMR (400 MHz,CDCl₃) δ ppm: 7.83-7.79 (m, 2H), 7.37-7.34 (m, 2H), 4.26-4.22 (m, 1H),4.15-4.12 (m, 1H), 3.98-3.93 (m, 1H), 2.46 (s, 3H), 1.85-1.81 (m, 1H),1.74-1.68 (m, 1H), 1.20 (m, 3H); ES-LCMS m/z: 245.2 [M+H]⁺.

Intermediate 12: Acetonyl 4-methylbenzenesulfonate

Acetonyl 4-methylbenzenesulfonate was prepared in a similar way asintermediate 8 using the corresponding starting material of1-hydroxypropan-2-one in 25.31% yield as a colorless oil. ¹H NMR (400MHz, CDCl₃) δ ppm: 7.82 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 4.48(s, 2H), 2.46 (s, 3H), 2.22 (s, 3H); ES-LCMS m/z: 229.2 [M+H]⁺.

Other 2-aminoquinoline derivatives were prepared in a similar way asthat described in Examples 1-7, and they are listed in Table 1. Thesecompounds were prepared in HCl salt forms, and/or in the forms ofneutral amine. A person skilled in the art can clearly understand andknow that the other analogs could be prepared by the same or similarmethods as described in Examples 1-7. These examples are not in any wayto limit the analogs that can be made by applying the same or similarmethods presented herein.

TABLE 1 2-Amino-Quinoline Derivatives Prepared Cmpd No. Structure 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

The compound functionality was tested for some of the compounds preparedby stimulation and determination of cytokine production in PBMCs.

Human PBMCs were prepared from buffy coat obtained from healthyvolunteer donor by Ficoll centrifugation and were adjusted to the finalcell concentration to 1×10⁶ cells/mL.

For evaluation of compound activities, 1×10⁵ PBMCs were plated in a96-well plate in 100 μl of RPMI 1640 complete medium (cat no. 31800-022,GIBCO by Life Technologies, Grand Island, N.Y., USA) supplemented with10% fetal bovine serum, the tested compound was first dissolved in DMSOand further diluted in PBS and RPMI 1640 medium to the finalconcentration of 20 μM (corresponding to 6.28 μg/mL), then 3-foldserially dilution was made in a 96-well round-bottom plate. 100 μldiluted compound was added to the same volume of 1×10⁵ PBMCs plate andcultured for 20-22 hours at 37° C. in a humidified atmosphere of 5% CO₂.The supernatant was collected for human IFN-α, IL12 (p70) and IL-6analysis by ELISA assay according to the manufacturer's instructions(Mabtech AB, Sweden). Resiquimod was used as a positive control.

Table 2 below lists the testing results on the evaluation of cytokineproduction for most of the compounds prepared.

TABLE 2* Compound Production of IFNa Production of IL-6 No. StructureM.W. on PBMC* on PBMC* 1

344.41 + + 2

328.41 + + 3

344.41 − − 4

330.38 − − 5

344.41 + + 6

328.41 N/A + 7

330.38 N/A + 8

316.35 + + 9

344.41 N/A + 10

358.43 N/A + 11

344.41 + + 12

400.51 + + 13

358.43 + + 14

358.43 + + 15

314.38 + + 16

358.43 + + 17

342.44 + + 18

328.41 + + 19

407.49 + + 20

437.51 + + 22

421.51 + + 23

595.86 + + 24

385.46 + + 25

609.89 + + 27

342.39 + + 28

341.41 + + 29

355.43 + + 31

270.33 − − 32

340.46 − − 33

326.44 − + 34

567.81 + + 35

581.83 + + 36

329.40 + + 37

314.38 + + 38

344.41 + + 39

284.31 + + 40

342.39 N/A − 41

342.39 N/A + 42

328.37 + + 43

328.37 N/A − 44

314.34 N/A − 45

314.34 N/A + 46

312.32 N/A + *Note 1: All the compounds were tested at concentration of10 μM. Note 2: “+” means that there was production of IFNa or IL-6 onPBMC; while “−” means that no production of IFNa or IL-6 on PBMC wasdetected.

What is claimed is:
 1. A compound represented by a formula:

or a salt thereof; wherein a dashed line represents the presence orabsence of a bond; A¹ is CR¹, NR^(1A), or N; A² is CR², NR^(2A), O, orS; B¹ is CR⁵ or N; B² is CR⁶ or N; B³ is CR⁷ or N; R¹ and R² areindependently F, CI, Br, I, NO₂, CN, R^(a), —OR^(a), —NR^(a)R^(b), —NHCOR^(a), —NHSO₂R^(a), —OCOR^(a), or —SO₂R^(a); X is a bond, O, NR^(a),—CO—, —SO—, or —SO₂—, —CONR^(a), hydrocarbonyl, and R³ is H or C₁₋₃₀organyl; or X—R³ is F or Cl; R^(1A), R^(2A), R⁴, R^(a), and R^(b) areindependently H or C₁₋₃₀ organyl; R⁵, R⁶, and R⁷ are independently F,Cl, Br, I, NO₂, CN, R^(a), —OR^(a), —NR^(a)R^(b), —NHCOR^(a),—NHSO₂R^(a), —OCOR^(a), —SO₂R^(a), —SO₂NHR^(a), or—X¹—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)),—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein R⁵ and R⁶ or R⁶ and R⁷ canbe optionally linked to form a ring; wherein X¹ is a bond, O, NR^(a),—CO—, —SO—, or —SO₂—; Z is a bond, O, NHSO₂, or NHCO; m is 0, 1, 2, 3,4, 5, 6, 7, 8, 9, or 10; and n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or
 23. 2. The compound of claim1, represented by a formula:

or a salt thereof, wherein R³ is C₁₋₃₀ organyl.
 3. The compound of claim1, represented by a formula:

or a salt thereof; wherein R⁴ is H, C₁₋₃₀ non-aromatic organyl, or C₁₋₃₀aromatic organyl containing an aromatic group that is not directlyattached to the N atom.
 4. The compound of claim 1, wherein R¹ or R^(1A)is C₁₋₁₂ optionally substituted alkyl.
 5. The compound of claim 4,wherein R¹ or R^(1A) is —C_(r)H_(2r+1)O, or an ester thereof, wherein ris 1, 2, 3, 4, 5, 6, 7, 8, 9, or
 10. 6. The compound of claim 5, whereinR¹ or R^(1A) is —C₃H₇O.
 7. The compound of claim 6, wherein R¹ or R^(1A)is —CH₂OCH₂CH₃.
 8. The compound of claim 1, wherein R² or R^(2A) is H orC₁₋₁₂ optionally substituted alkyl.
 9. The compound of claim 8, whereinR² or R^(2A) is C₁₋₆ alkyl, or —C_(y)H_(2y+1)O or an ester thereof,wherein y is 1, 2, 3, 4, 5, 6, 7, 8, 9, or
 10. 10. The compound of claim9, wherein R² or R^(2A) is CH₃.
 11. The compound of claim 8, wherein R²or R^(2A) is H.
 12. The compound of claim 8, wherein R² or R^(2A) isC₄H₉.
 13. The compound of claim 1, wherein R³ is C₁₋₃₀ optionallysubstituted alkyl.
 14. The compound of claim 13, wherein R³ is C₁₋₁₀alkyl, or —C_(w)H_(2w+1)O or an ester thereof, wherein w is 1, 2, 3, 4,5, 6, 7, 8, 9, or
 10. 15. The compound of claim 1, wherein R³ is—(C_(t)H_(2t)O₀₋₁)-Ht, wherein t is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10,and Ht is optionally substituted C₃₋₆ heterocyclyl.
 16. The compound ofclaim 1, wherein R³ is —(C_(u)H_(2u)O₀₋₁)—Z—(C_(v)H_(2v+1)), wherein Zis a bond, O, NHSO₂, or NHCO, u is 0, 1, 2, 3, 4, 5, or 6, and v is 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, or
 23. 17. The compound of claim 1, wherein R³ is—(C_(u)H_(2u)O₀₋₁)—NR^(a)R^(b), and u is 1, 2, 3, 4, 5, or 6, whereinR^(a) and R^(b)are independently H or C₁₋₆ alkyl.
 18. The compound ofclaim 14, wherein R³ is C₅H₁₁O.
 19. The compound of claim 14, wherein R³is —CH₂—CH₂—CH(CH₃)₂OH.
 20. The compound of claim 17, wherein R³ is—CH₂—CH₂—CH₂—NH₂.
 21. The compound of claim 1, wherein R⁴ is H or C₁₋₆alkyl.
 22. The compound of claim 21, wherein R⁴ is H.
 23. The compoundof claim 1, wherein R⁵ is R^(a), F, Cl, —CO₂R^(a), —CONR^(a)R^(b), CN,—OR^(a), —NR^(a)R^(b), —OCOR^(a), or —SO₂R^(a), —SO₂NHR^(a), whereinR^(a) and R^(b) are independently H or C₁₋₆ alkyl.
 24. The compound ofclaim 23, wherein R⁵ is H.
 25. The compound of claim 1, wherein R⁵ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, NHSO₂, orNHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24or
 25. 26. The compound of claim 1, wherein R⁶ is R^(a), F, Cl,—CO₂R^(a), —CONR^(a)R^(b), CN, —OR^(a), —NR^(a)R^(b), —OCOR^(a), or—SO₂R^(a), —SO₂NHR^(a), wherein R^(a) and R^(b) are independently H orC₁₋₆ alkyl.
 27. The compound of claim 26, wherein R⁶ is H.
 28. Thecompound of claim 1, wherein R⁶ is —(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)),wherein Z is a bond, O, NHSO₂, or NHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8,9, or 10, and n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, or
 23. 29. The compound of claim 1, whereinR⁷ is R^(a), F, Cl, —CO₂R^(a), —CONR^(a)R^(b), CN, —OR^(a),—NR^(a)R^(b), —OCOR^(a), or —SO₂R^(a), —SO₂NHR^(a), wherein R^(a) andR^(b) are independently H or C₁₋₆ alkyl.
 30. The compound of claim 29,wherein R⁷ is H.
 31. The compound of claim 1, wherein R⁷ is—(C_(m)H_(2m)O₀₋₁)—Z—(C_(n)H_(2n+1)), wherein Z is a bond, O, NHSO₂, orNHCO, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, and n is 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23.32. The compound of claim 1 to 31, R⁸ is H, OH, or CH₃.
 33. The compoundof claim 32, wherein R⁸ is OH.
 34. The compound of claim 32, wherein R⁸is H.
 35. The compound of claim 1, which is:

a salt of any of these compounds, or an ester of any of these compoundshaving an —OH group.
 36. The compound of claim 1 which is optionallysubstituted 9-methoxy-1H-imidazo[4,5-c]quinolin-4-amine.
 37. Thecompound of claim 1 which is optionally substituted9-methoxy-2H-pyrazolo[3,4-c]quinolin-4-amine.
 38. The compound of claim36, which is optionally substituted1-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-isobutyl-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-(4-amino-9-methoxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted1-(4-amino-2-(2-hydroxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1H-imidazo[4,5-c]quinolin-4-amine or asalt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butan-2-olor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted4-((4-amino-2-(ethoxymethyl)-1-isobutyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-1-(2-isopropoxyethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted4-(4-amino-2-(ethoxymethyl)-9-methoxy-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylbutan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1H-imidazo[4,5-c]quinolin-4-amine or a saltthereof; optionally substituted2-(ethoxymethyl)-9-(2-isopropoxyethoxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-(isopentyloxy)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isobutoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)methanesulfonamideor a salt thereof; optionally substitutedN-(2-(2-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)ethoxy)ethyl)-methanesulfonamideor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)acetamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)methanesulfonamideor a salt thereof; optionally substitutedN-(34(4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)stearamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)acetamideor a salt thereof; optionally substitutedN-(4-(4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)-stearamideor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(2-morpholinoethoxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-((tetrahydrofuran-3-yl)oxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(pyrrolidin-3-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-1-methyl-9-(piperidin-4-yloxy)-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substitutedN-(3-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)propyl)palmitamideor a salt thereof; optionally substitutedN-(4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)butyl)palmitamideor a salt thereof; optionally substituted9-(3-aminopropoxy)-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted2-(ethoxymethyl)-9-isopropoxy-1-methyl-1H-imidazo[4,5-c]quinolin-4-amineor a salt thereof; optionally substituted1-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)-2-methylpropan-2-olor a salt thereof; optionally substituted2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-10-amineor a salt thereof; optionally substituted(R)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-(10-amino-2-(ethoxymethyl)-3,4-dihydro-5-oxa-1,2a,9-triazanaphtho[2,1,8-cde]azulen-3-yl)propan-2-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6-methyl-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(R)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted(S)-2-amino-12-(ethoxymethyl)-6,7-dihydro-5H-3,4-(azenometheno)[1,5]oxazocino-[4,3,2-de]quinolin-6-olor a salt thereof; optionally substituted2-amino-12-(ethoxymethyl)-5H-3,4-(azenometheno)[1,5]oxazocino[4,3,2-de]quinolin-6(7H)-oneor a salt thereof; or optionally substituted tert-butyl4-((4-amino-2-(ethoxymethyl)-1-methyl-1H-imidazo[4,5-c]quinolin-9-yl)oxy)piperidine-1-carboxylateor a salt thereof.
 39. The compound of claim 37, which is optionallysubstituted 4-amino-2H-pyrazolo[3,4-c]quinolin-9-ol or a salt thereof;optionally substituted4-amino-2-isopentyl-2H-pyrazolo[3,4-c]quinolin-9-ol or a salt thereof;optionally substituted2-isopentyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or asalt thereof; or optionally substituted2-butyl-9-(isopentyloxy)-2H-pyrazolo[3,4-c]quinolin-4-amine or a saltthereof.
 40. A method of treating viral infection, cancer, or anallergic disease, comprising administering a compound of claim 1, to amammal in need thereof.
 41. (canceled)
 42. The method of claim 40,wherein the viral infection comprises HCV infection.
 43. A dosage formsuitable for administration to a mammal, comprising a compound of claim1.